Aerosol generating and delivery device

ABSTRACT

Particular aspects provide novel atomizers for generating particles over a broad range of MMAD size distributions, the eliminating the requirement for an impaction baffle in generating the desired particle sizes. In particular aspects, the atomization means communicates with a remote particle filter member configured and positioned to provide for particle size filtering. In additional aspects, the atomization means communicates with a particle dispersion chamber suitable to impart a desired particle flow pattern to particles within and exiting the dispersion chamber. In further aspects, the atomization means communicates with a nasal, ocular, oral or ‘vicinity’ adapter. The novel devices provide for targeted (e.g., nasal, ocular, oral, local vicinity), systemic, and/or topical delivery of an atomized liquid (e.g., via the nasal cavity, olfactory region, and mouth). Further exemplary aspects relate to aerosolization and delivery of perfume, fragrance, essential oil or cosmeceutical agents and the like.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.11/848,225 (Issuing as U.S. Pat. No. 7,905,229) filed 30 Aug. 2007,which claims the benefit of priority to U.S. Provisional PatentApplication Ser. No. 60/824,017, filed 30 Aug. 2006, both of which areincorporated by reference herein in their entirety.

FIELD OF THE INVENTION

Particular exemplary aspects relate generally to aerosolized particlegeneration and delivery of same to a user, and more particularly tonovel devices and apparatus for atomized particle generation, and tonovel integrated particle generation, dispersion and delivery devicessuitable for targeted delivery to a user including, but not limited tothe nasal cavity or regions thereof of a user, the inside of the mouthof a user, the skin of the user, the surface of the eye of a user, andthe vicinity of a user. Additional exemplary aspects relate to novelmethods for administration of therapeutic agents to the nasal cavity,deep nasal cavity and paranasal sinuses of a user (e.g., a patient)using the novel devices, and to ocular and oral delivery using the noveldevices. Further exemplary aspects relate to aerosolization and deliveryof perfume, fragrance, essential oil or cosmeceutical agents and thelike.

BACKGROUND

In the United States, sixty million people suffer from chronic sinusitisand allergic rhinitis and are treated by means of topically appliedantihistamines, antibiotics, decongestants, and pain relievers. Many ofthese drugs would work more effectively in relieving symptoms if theycould be applied directly to all of the affected areas. However, thedevices utilized thus far to deliver these drugs have proven to beextremely inadequate, if not useless, in reaching all areas neededespecially the deep nasal cavity, olfactory region, and paranasalsinuses critical to the treatment of some of these diseases andconditions. In addition to topically applied drugs (e.g., such asparticular drugs in the categories listed above), there are a widevariety of systemically-absorbed drugs that are delivered intranasally.Moreover, a completely new field of nose to brain drug delivery isemerging. Current devices utilized for such systemically-absorbed drugshave also proven to be inadequate for many applications.

Current delivery systems comprise, for example, metered dose spraybottles and pneumatic (e.g., compressed air) atomizers that eject themedicine into the nostrils in large particles, or streams of atomizedliquid. While a substantial mass of aerosolized particles can be quicklyejected or projected from such devices, the ejected or projectedparticles are relatively large, such that the efficacy of medicineadministered in this manner is limited because of variable user skilland inadequate delivery and/or target distribution. For example, becauseof the relatively large particle sizes and the velocity vectors andcharacteristics of the particles, medicines delivered in this mannerreach very little of the nasal mucosa and essentially no part ofparanasal sinuses. Instead, such devices spray the particles into, forexample, the anterior nasal cavity where the substantial mass of theparticles impact the surfaces and drip out the nostril, or quickly clearalong the floor of the nasal cavity. In cases of severe congestion ornasal polyps, the medicine often does not proceed beyond the nostril andhas no chance of being effectively absorbed into the bloodstream in thenecessary area of the nasal cavity. Therefore, while current prior artmetered dose spray bottles and pneumatic atomization systems allow forrapid mass delivery, they are typically of relatively crude simplisticdesign, and substantially waste medicament because they do not provideadequate particle size distributions or delivery targeting for manypurposes (e.g., they do not allow for particles to penetrate or reachhigh into the nasal cavity, and be retained therein, as required forsystemic nose to brain delivery, or for paranasal sinus delivery.

As an improvement, pneumatic (e.g., compressed air) nebulizers have beendeveloped and are familiar in the art. Fundamentally, nebulizers aredistinguished from simple atomizers by the presence in the former of an‘impaction or stagnation baffle’ placed, adjacent the compressed gasorifice, in the aerosol stream. Typically, for pneumatic nebulizers,compressed gas is delivered through a compressed air channel and orifice(jet) of a compound integrated aerosolization nozzle causing a region ofnegative pressure (Venturi effect) in close proximity to a restrictedliquid/solution channel or capillary. The liquid to be aerosolized isentrained, by virtue of its proximity to the restricted liquid channelwithin the nozzle configuration, into the jet orifice gas stream and issheared into a liquid film or ligaments that may collapse into initialdroplets under the influence of surface tension. While a smallproportion of the initial droplets are smaller (e.g., 5 μm or less), thepredominant portion of such initial droplets and/or film/ligaments aresubstantially larger and are subsequently violently shattered uponimpaction with the closely spaced impaction/stagnation baffle, whichserves to provide for production of smaller droplets and for return oflarger droplets to the liquid reservoir. For efficacy in optimizingsmaller particle production, the impaction/stagnation baffle is placedextremely close to the compressed air orifice, typically within afraction of a millimeter from the jet or nozzle orifice. Because of theclose spacing, the impaction/stagnation baffle also serves to redirectcompressed gas flow laterally toward the walls of the atomizationchamber, and smaller particles (e.g., 5 μm or less, corresponding toboth shattered and initially atomized small unshattered particles) arethereby carried laterally toward the walls of the nebulization chamber.While most of such laterally directed particles are thereaftercollisionally ‘consumed’ by walls/surfaces of the atomization chamber, asmall proportion of such laterally-directed particles are againredirected toward the user by the user's inhalation stream and arethereby rendered deliverable to the user (e.g., deliverable as a mist orvapor of very tiny particles to the lungs by means of a user breathingthe medicine-containing particles from a pipe attachment or, in the caseof young children, a face mask, e.g., inhalation of nebulized particlesduring an asthma attack).

Therefore, prior art closely spaced impaction/stagnation baffles providetwo functions: (i) shattering of larger particles into smallerparticles; and (ii) laterally redirecting smaller particles. However, ineither instance, the deliverable particles do not have, upon generation,a velocity vector path in the direction of the user that is notobstructed by the impaction/stagnation baffle, and the particle velocityvectors are such that the particles thus either impact on the baffle,laterally impact on the atomization chamber wall/surfaces, or arelaterally directed and subsequently directed toward the user.Significantly, therefore, with prior art nebulizers, there are noparticles that have, as initially generated, velocity vectors with pathstoward the user that are not obstructed by the impaction/stagnationbaffle, and delivery of such particles is thus entirely dependent uponredirecting particles around the baffle by inhalation facilitated flowredirection. Significantly therefore, not only is the size range ofdeliverable particles limited by such designs (e.g., to those smallenough to be laterally directed and redirected toward the user (e.g., 5μm or less) by the inhalation stream, but the delivery efficiency islimited because of the small percentage of particles that avoid being‘consumed’ on the baffle, and on the walls and surfaces of theatomization chamber because of the indirect paths that the deliverableparticles must take. This is a significant limitation of prior artdevices.

Fundamentally, with prior art pneumatic nebulizers, while theimpaction/stagnation baffle serves to redirect the compressed air flowdirection (typically at right angles to the longitudinal jet axis) andreturn larger droplets to the liquid reservoir for re-entrainment, thecreation and size of the generated deliverable particles are entirelydetermined by violent impaction with the baffle subsequent toentrainment of the solution by the compressed air jet of the nozzle, andthose shattered particles that don't then impact the side-walls aredrawn to the user during user inhalation. Droplet size is typicallyreported as mean mass aerodynamic diameter (MMAD), which is the diameteraround which the mass of the aerosol is equally divided; that is, thecalculated aerodynamic diameter that divides the particles of an aerosol(a gaseous suspension of fine liquid or solid particles) in half, basedon the mass of the particles (by mass, 50% of the particles will belarger than the MMAD and 50% of the particles will be smaller than theMMAD). Therefore MMAD is used to characterize a population of dropletsproduced, and does not refer to the size of individual droplets. Theparticle size distribution of any aerosol may thus be statisticallydescribed by the median aerodynamic diameter along with the geometricstandard deviation (GSD) based on the weight and size of the particles.Significantly, it should be appreciated, that because the volume (andhence the mass) of the droplet is determined by the cube of the radius(v=4/3πr³), most of the particles will be smaller than the MMAD. Therespirable dose is sometimes reported as the respirable mass, which isthe output of droplets from the nebulizer in, for example, a respirablerange of 1-5 um. Therefore, with prior art pneumatic nebulizers, thesize and output of droplets comprising the respirable mass is entirelydetermined by the impaction and shattering function of the closelyopposed impaction/stagnation baffle, and where a small but deliverableproportion of the laterally-directed particles avoid impacting theside-walls of the atomization chamber and are rather carried to the userin the user's inhalation stream.

Typically, a device selected for administration of pharmacologicallyactive aerosol to the lung parenchyma should produce particle sizes witha mass median aerodynamic diameter (MMAD) of 1-3 microns. For airwaydeposition MMAD should be around 2-5 microns. Relatively small particlesize is important for lung delivery in that, for example, it allowspassage of the drug through heavily congested airways over a sufficientperiod (e.g., of about 10 minutes), to allow for deep lung penetration.Such nebulizers are used, for example, by asthmatics in response to anasthma attack.

With reference to FIG. 1, such prior art pneumatic nebulizers generallyhave, in addition to a closely opposed impaction element/baffle, acompound integrated aerosol nozzle comprising a compressed air or fluidchannel with an end orifice, along with an integrated solution channelin communication with a liquid or solution (e.g., medicine solution).Moreover, such nebulizers generally correspond to one of two types;namely an ‘internal mixing’ (FIG. 1A) design or an ‘external mixing’(FIG. 1B) design (see, e.g., Hess, D. R., Respriatory Care, 435:609-622,2000 for a discussion of nebulizer designs incorporated herein byreference). Generally speaking, with internal mixing designs, gas flowinteracts with the solution prior to leaving the nozzle exit orifice.For example, in FIG. 1A, the nozzle is concentrically mounted around acompressed gas delivery tube/channel (with end orifice) such thatbetween the tube and nozzle there is a narrow interspace channel incommunication with a liquid/solution reservoir. The exit of compressedgas from the gas delivery tube orifice causes solution to be drawn upthrough the restricted interspace to form an ascending stream of air andsolution which leaves from the nozzle orifice and strikes the baffle tocause atomization of the particles (see also FIG. 1 of U.S. Pat. No.6,796,513). By contrast, with external mixing, jet gas and the solutioninteract after both leave the nozzle. For example, in FIG. 1B, thenozzle orifice is a compound orifice, comprising a gas deliverytube/channel (with end orifice) that is coplanar with respect to aconcentric solution channel orifice. In such designs fluid must leavethe solution channel orifice (and the nozzle) before it can interactwith the jet gas. The exit of compressed gas from the gas delivery tubeorifice (and thus from the nozzle) causes solution to be drawn from thenarrow solution channel and orifice (and thus from the nozzle) where itsubsequently interacts with the jet gas to form a stream of air andsolution which strikes the baffle to cause atomization of the particles.Different jet nebulizers have different output characteristicsdetermined by the design of the air jet and capillary tube orifices,their geometric relationship with each other and with the closelyopposed impaction baffles. In such prior art configurations, the majoroutput determinant is generally the level/strength of the driving gasflow. So-called open ‘vented’ versions of these nebulizer designs allowfor intake of ambient air during user inhalation to increase particleflow to the user and thus increase, at least to some extent, theeffective nebulizer output at least during the inhalation phase.

Unfortunately, conventional jet nebulizers, including open ventedversions, are highly inefficient because much of the aerosol is wastedduring exhalation or excessively recycled within the nebulizer. Inparticular nebulizer designs, some aerosol waste is prevented by havingone-way valves near the mouthpiece that redirect exhalation so that isdoes not substantially exhaust through the open inhalation vent in theprimary aerosol generation chamber. However, even in these designs,between 93 and 99% of the primary droplets are caught on the internalbaffles and structures and typically returned to the solution reservoirfor re-entrainment, resulting in low output and/or protractednebulization times. Additionally, in view of the pervasive use ofrestricted or narrow liquid feed channels to the medicament reservoirsmeans, while prior art atomizers and nebulizers are adequate forgenerating particles from low viscosity solutions (e.g., up to 5centipoise), they are incapable of delivery of more viscous solutions(e.g., 5-105 centipoise). Thus, most such currently used nebulizers arenot sufficiently effective at delivering enough medicament formulation(especially viscous drug solutions) in a practical or reasonabletime-period because of restrictive liquid feed channels and therequirement for impaction/stagnation baffle configurations to shatterand size the particles. Additionally, even if more powerful compressormeans were to be employed in such designs, there would be attendantincreases in device size, weight and expense, and also (at least inparticular designs) an increase the aerosol waste during exhalationphases. Moreover, increased compressed air flow would not eliminate theexcessive 93 to 99% recycling of impacted medicine droplets returned tothe solution reservoir from the impaction baffles. Additionally, even ifthere was an amount and/or quality of output sufficient for particledelivery to the lungs, absent an appropriate particle generation anddispersion means (as taught herein below by applicants), such prior artnebulizers are not effective for nasal delivery of drugs (e.g.,antibiotics, etc.), because the generated particles are (i) notappropriately sized or dispersed to effectively penetrate into the nasalcavity and/or paranasal sinuses, and (ii) not delivered in a direct flowpath to enable efficient delivery of sufficient quantities of medicamentin a practical time-frame.

There is, therefore, a pronounced need in the art for delivery methodsand devices that enable more efficient output and delivery ofaerosolized particles. There is a pronounced need for devices thatreduce or eliminate the dependence on baffle impaction and flowredirectioning for generation and determination of particle size, notonly to reduce the extent/amount of recycling and re-entrainment ofbaffle-impacted solution droplets to allow for shorter, moreuser-friendly delivery periods, but also to provide for generation of abroader range of particle sizes to enhance dynamic output.

There is a pronounced need in the art for more effective methods anddevices for delivery of aerosolized medicaments of higher viscosity.

There is a pronounced need in the art for more effective methods anddevices for delivery of medicament to treat patients for certainconditions without taking the medicament orally or through the lungs.There is a pronounced need for more effective and efficient delivery toall areas of the nasal cavity and paranasal sinuses, and for morestrategic or targeted delivery of medicament to specific regions of thenasal cavity, nasal olfactory region and paranasal sinuses. There is apronounced need in the art for more effective methods and devices toeffectively administer therapeutic agents systemically via the nasalpassages, through the various channels from the olfactory region to thebrain and the deep paranasal sinuses. There is a pronounced need formore effective methods and devices to for delivery of drugs to the brainto treat conditions of the central nervous system (CNS); that is, for‘Nose-to-Brain’ delivery (e.g., to bypass the so-called blood brainbarrier). There is a pronounced need for ocular and oral delivery usingmore efficient devices, and more efficient means for aerosolization anddelivery of perfume, fragrance, essential oil or cosmeceutical agentsand the like to the vicinity or surfaces or users or targets.

SUMMARY OF THE INVENTION

Particular aspects generally provide novel particle generating devices,and in more particular aspects, novel, more efficient atomizationdevices that are capable of atomizing and effectively deliveringliquids, and particularly those having increased viscosity relative tothose liquids usable with prior art nebulization and atomizationdevices.

Additional aspects provide particle generation and delivery devicescomprising the novel particle generating apparatus in combination with aconduit for delivering of the airborne (e.g., atomized) particles.Preferably, the inventive particle generation and delivery devices arefor delivery of appropriately sized aerosolized particles to a user, andpreferably delivery is to the nasal cavity, or region thereof, of theuser by means of a nasal adapter, or for oral or ocular delivery.

Additional aspects provide novel integrated devices and apparatuscomprising novel particle generation means (e.g., atomization), particledispersion chamber, and adapter means for targeted delivery ofaerosolized dispersed particles to a user, and preferably to the nasalcavity or regions thereof of the user. Preferably, the integrateddevices are suitable for the targeted administration of therapeuticagents to the nasal cavity and paranasal sinuses of a patient. Inpreferred embodiments, such integrated devices comprise, in addition toparticle generation and dispersion means, an aerodynamic ‘particle sizefilter’ or ‘splitter’ and a nasal, oral or ocular adapter.

According to preferred aspects, particle size, velocity characteristicsand nostril entry location determine whether a majority of a medicamentwill reach a productive target area (e.g., deep nasal cavities,olfactory region, paranasal sinuses, etc.), or unproductively impact anddeposit in the nasal aperture to drip back down the nose with minimalproductive delivery and deposition in the nasal cavity.

Particular aspects provide an aerosol generating device comprising: anupright liquid feed tube having a liquid exit orifice and a sidewall;and an upright compressed fluid feed channel having a compressed fluidexit orifice, the compressed fluid exit orifice being spaced from aportion of the sidewall, the compressed fluid exit orifice beingconfigured to direct a stream of compressed fluid toward the portion ofthe sidewall, the portion of the sidewall being configured to disrupt aportion of the stream of compressed fluid, the disrupted portion of thestream of compressed fluid being configured to atomize a liquid from theliquid exit orifice. In certain aspects, the atomized liquid comprisesparticles, and the device further comprises a filtering memberconfigured aerodynamically to filter particles from the atomized liquidhaving a size greater than a predetermined maximum size. Particularembodiments further comprise a particle dispersion chamber configured toreceive the atomized liquid and impart a predetermined flow patternthereto. In certain aspects, the predetermined flow pattern is vortical.In certain embodiments, the upright liquid feed tube comprises a liquidsupply member comprising a liquid feed channel, the feed channel havingan inlet, a liquid supply member exit orifice, and a supply memberend-wall face having an outside diameter disposed about the liquidsupply member exit orifice, the liquid supply member feed channeldefining a projected axis L, wherein the end wall face liquid feedchannel exit orifice is separated by a distance of at least H from thecompressed fluid channel exit orifice, H being measured along aprojected axis F that is normal to a plane P defined by the compressedfluid channel exit orifice, H is equal to or greater than ¼, ½ or 1× theinner diameter D1 of the compressed fluid channel adjacent thecompressed fluid channel exit orifice, the projected longitudinal axis Lintersects the projected axis F at a right, acute or obtuse angle,defining an intersection plane I, and wherein at the distance H alongprojected axis F, the plane I-intersecting portion of the perimeter ofthe end-wall face is positioned at a distance S in a normal directionfrom the projected axis F, S being equal to or less than 2× the innerdiameter D1 of the primary compressed fluid channel. In certain aspects,the liquid comprises at least one selected from the group consisting ofmedicaments, small or large molecule pharmaceutical agents, liquids,solutions, suspensions, emulsions, perfumes, fragrances, essential oils,cosmeceutical agents, oils, cosmeceutical agents, moisturizing agents,water, lotions, air fresheners, deionizing agents, aromatherapeuticagents, beverages, and skin treatments. In particular embodiments, thedevice further comprises a nasal, ocular, oral or ‘vicinity’ adapter incommunication with the atomization means.

Additional embodiments provide an aerosol generating device comprising:a reservoir configured to hold a liquid; a liquid supply membercomprising a diverting portion and a feed channel, the feed channelhaving an inlet in communication with the reservoir and an liquid supplymember exit orifice, the feed channel being configured to draw liquidfrom the reservoir and transport it to the exit aperture foraerosolization therefrom by a compressed fluid; and a compressed fluidsupply member comprising a compressed fluid channel having an exitorifice, the diverting portion being located between the exit orifice ofthe feed channel and the exit orifice of the compressed fluid channel,the compressed fluid channel being configured to receive a compressedfluid and conduct a portion of the compressed fluid through the exitorifice and into engagement with the diverting portion of the liquidsupply member, the portion of the compressed fluid engaging thediverting portion being diverted by the diverting portion beforeaerosolizing the liquid from the exit aperture of the feed channel. Incertain aspects, the compressed fluid channel and the diverting portionare configured such that a second portion of the compressed fluidconducted through the compressed fluid exit orifice does not engage thediverting portion of the liquid supply member. In particularembodiments, the diverting portion has a surface, the portion of thecompressed fluid engaging the diverting portion engages the surface ofthe diverting portion, and the surface is configured to divert theportion of the compressed fluid engaging it non-uniformly. In certainaspects, the liquid supply member comprises a tube section, the feedchannel comprises a first portion disposed inside the tube section, theexit aperture of the feed channel is formed in the tube section, and thetube section comprises an outside surface, and the diverting portioncomprises a portion of the outside surface of the tube section locatedbetween the exit orifice of the feed channel and the exit orifice of thecompressed fluid channel. In some embodiments, the portion of thecompressed fluid conducted through the compressed fluid exit orificeexits the orifice along an axis “F,” the liquid feed channel has alongitudinal axis “L,” and the axis “F” intersects the axis “L.” Inparticular aspects, the liquid supply member comprises an anchor portionand a free end portion, the anchor portion is located between the inletof the liquid supply member and the exit orifice of the liquid supplymember, the anchor portion is coupled to the compressed fluid supplymember; and the free end portion comprises the inlet of the liquidsupply member and is supported by the anchor portion within thereservoir. In some embodiments, the device further comprises a particledispersion chamber configured to impart a flow pattern to theaerosolized liquid. Particular embodiments comprise a supply memberend-wall face having an outside diameter disposed about the liquidsupply member orifice, wherein the liquid supply member feed channeldefines a projected axis L, the end wall face and the orifice areseparated by a distance of at least H from compressed fluid channel exitorifice, H being measured along a projected axis F that is normal to aplane P defined by the compressed fluid channel exit orifice, H is equalto or greater than ¼, ½ or 1× the inner diameter D1 of the compressedfluid channel adjacent the compressed fluid channel exit orifice, theprojected longitudinal axis L intersects the projected axis F at aright, acute or obtuse angle, defining an intersection plane I, andwherein at the distance H along projected axis F, the planeI-intersecting portion of the perimeter of the end-wall face ispositioned at a distance S in a normal direction from the projected axisF, S being equal to or less than 2× the inner diameter D1 of the primarycompressed fluid channel. In certain aspects, the liquid for which thereservoir is configured to hold comprises at least one selected from thegroup consisting of medicaments, small or large molecule pharmaceuticalagents, liquids, solutions, suspensions, emulsions, perfumes,fragrances, essential oils, cosmeceutical agents, oils, cosmeceuticalagents, moisturizing agents, water, lotions, air fresheners, deionizingagents, aromatherapeutic agents, beverages, and skin treatments. Certainembodiments further comprise a nasal, ocular, oral or ‘vicinity’ adapterin communication with the atomization means.

Yet additional embodiments provide an aerosol generating devicecomprising: a reservoir configured to hold a liquid; a liquid supplymember comprising a feed channel comprising: a first portion with afirst diameter and an exit orifice, and a second portion with a seconddiameter and an inlet aperture in communication with the reservoir, thefirst portion diameter being smaller than the second portion diameter,the feed channel being configured to draw liquid from the reservoir intothe inlet aperture of the second portion and transport it to the exitorifice of the first portion for aerosolization therefrom by acompressed fluid; and a compressed fluid supply member comprising acompressed fluid channel and compressed fluid channel exit orificeconfigured to direct a compressed fluid flow passed the exit orifice ofthe first portion of the feed channel thereby aerosolizing the liquidtherefrom. In certain aspects, the liquid held in the reservoir has asurface, at least a portion of the liquid supply member is locatedinside the reservoir, a first section of the second portion is below thesurface of the liquid, and a second section of the second portion isabove the surface of the liquid. Particular embodiments comprise asupply member end-wall face having an outside diameter disposed aboutthe liquid supply member orifice, wherein the liquid supply member feedchannel first portion defines a projected axis L, the end wall face andthe orifice are separated by a distance of at least H from compressedfluid channel exit orifice, H being measured along a projected axis Fthat is normal to a plane P defined by the compressed fluid channel exitorifice, H is equal to or greater than ¼, ½ or 1× the inner diameter D1of the compressed fluid channel adjacent the compressed fluid channelexit orifice, the projected longitudinal axis L intersects the projectedaxis F at a right, acute or obtuse angle, defining an intersection planeI, and wherein at the distance H along projected axis F, the planeI-intersecting portion of the perimeter of the end-wall face ispositioned at a distance S in a normal direction from the projected axisF, S being equal to or less than 2× the inner diameter D1 of the primarycompressed fluid channel. In certain embodiments, the liquid for whichthe reservoir is configured to hold comprises at least one selected fromthe group consisting of medicaments, small or large moleculepharmaceutical agents, liquids, solutions, suspensions, perfume,fragrance, essential oil or cosmeceutical agents, oils, cosmeceuticalagents, moisturizing agents, water, lotions, air fresheners, deionizingagents and skin surface treatments. Certain aspects further comprise anasal, ocular, oral or ‘vicinity’ adapter.

Further embodiments provide an aerosolization device having anaerosolization assembly configured to produce a stream of aerosolizedparticles from a liquid stored in a reservoir, the device comprising: afiltering member spaced apart from the aerosolization assembly andlocated within the stream of aerosolized particles, the filtering memberbeing configured aerodynamically to separate the aerosolized particleswithin the stream of aerosolized particles having a size greater than apredetermined size from the aerosolized particles within the stream ofaerosolized particles having a size less than or equal to thepredetermined size, to collect the aerosolized particles having a sizegreater than a predetermined size and return them to the reservoir, andto permit the aerosolized particles having a size less than or equal tothe predetermined size to pass thereby. In certain embodiments, thefiltering member is configured aerodynamically to avoid collisions withthe aerosolized particles of the stream of aerosolized particles. Incertain aspects, at least 20%, at least 30%, at least 40%, at least 50%,or at least 60% of the aerosolized particles within the stream ofaerosolized particles pass by the filtering member without collidingtherewith. Particular aspects further comprise a particle dispersionchamber configured to receive the particles that pass by the filtermember and impart a predetermined flow pattern to the particles. Inparticular implementations, the aerosolization assembly comprises aliquid supply member comprising a liquid feed channel, the feed channelhaving an inlet in communication with the reservoir, an liquid supplymember exit orifice, and a supply member end-wall face having an outsidediameter disposed about the liquid supply member exit orifice, theliquid supply member feed channel defining a projected axis L, whereinthe assembly further comprises a compressed fluid supply membercomprising a compressed fluid channel having an exit orifice, whereinthe end wall face and liquid feed channel exit orifice are separated bya distance of at least H from compressed fluid channel exit orifice, Hbeing measured along a projected axis F that is normal to a plane Pdefined by the compressed fluid channel exit orifice, H is equal to orgreater than ¼, ½ or 1× the inner diameter D1 of the compressed fluidchannel adjacent the compressed fluid channel exit orifice, theprojected longitudinal axis L intersects the projected axis F at aright, acute or obtuse angle, defining an intersection plane I, andwherein at the distance H along projected axis F, the planeI-intersecting portion of the perimeter of the end-wall face ispositioned at a distance S in a normal direction from the projected axisF, S being equal to or less than 2× the inner diameter D1 of the primarycompressed fluid channel. In certain aspects, the liquid for which thereservoir is configured to hold comprises at least one selected from thegroup consisting of medicaments, small or large molecule pharmaceuticalagents, liquids, solutions, suspensions, emulsions, perfumes,fragrances, essential oils, cosmeceutical agents, oils, cosmeceuticalagents, moisturizing agents, water, lotions, air fresheners, deionizingagents, aromatherapeutic agents, beverages, and skin treatments.Particular aspects further comprise a nasal, ocular, oral or ‘vicinity’adapter in communication with the atomization means.

Particular aspects provide an aerosol generating and delivery device,comprising: a housing having a wall defining an atomization chamber inwhich a liquid or solution is atomizable, and having holding meanssuitable for holding a liquid or solution to be atomized; the devicefurther comprising atomization means comprising a primary compressedfluid feed channel having a length and inner diameter, and a primaryorifice at a first end thereof in fluid communication with theatomization chamber and defining a primary orifice plane “P”, thechannel at a second end in fluid communication with a compressed fluidsource and defining a projectable compressed fluid feed channel axis“F”, the atomization means further comprising a primary liquid feedchannel having a length, inner diameter and channel wall, and at a firstchannel end having a channel end-wall face having an outside diameterdisposed about a liquid feed channel orifice in fluid communication withthe atomization chamber, the primary liquid feed channel at a second endin communication with the liquid holding means, the primary liquid feedchannel defining a projectable longitudinal liquid feed channel axis“L”, wherein the channel end wall face and the liquid feed channelorifice are separated by a distance of at least H from the primaryorifice plane “P”, H being measured along the projected axis “F” and Hbeing equal to or greater than ¼, ½ or 1× of the inner diameter D1 ofthe primary compressed fluid feed channel, wherein the projectedlongitudinal axis “L” intersects the projected longitudinal axis “F” atan acute angle defining an intersection plane “I”, and wherein at thedistance “H” along projected longitudinal axis “F”, the plane“I”-intersecting portion of the perimeter of the end-wall face ispositioned at or within a selected normal distance S from the projectedlongitudinal axis “F”, S being equal to or less than 2× the innerdiameter D1 of the primary compressed fluid feed channel.

In additional aspects, the aerosol generating and delivery devicefurther comprises an aerodynamic particle size filter member in fluidcommunication with the particle atomization means, the filter memberhaving an aerodynamic surface contour and positioned at a distance “J”along the projected axis “F” from the primary orifice plane “P” toprovide an aerodynamic fluid flow around the surface, wherein thedistance “J” is greater than the distance “H”.

In further aspects, the aerosol generating and delivery device furthercomprises a particle dispersion chamber having a chamber wall and havingan input opening and an output opening with an internal channeltherebetween, the input opening in fluid communication with theatomization chamber, the dispersion chamber having at least one directedfluid output operative to impart a fluid flow pattern (e.g., ‘vortical’flow, turbulent flow or randomized flow) to aerosolized particles withinand exiting the dispersion chamber output opening.

In particular embodiments, the at least one directed fluid outputcomprises an ambient air channel that at one end is in communicationwith ambient air, and having at the other end an ambient air channelorifice in communication with the internal channel. In additionalembodiments, the aerosol generating and delivery device furthercomprises an outer housing having an outer housing wall defining aplenum space between the outer housing wall and the wall of the particledispersion chamber, the outer housing wall comprising at least oneopening (with optional one-way valve) in communication with ambient air,such that the ambient air channel and corresponding orifice communicatewith the at least one opening by means of the plenum space.

In some embodiments, the at least one directed fluid output comprises acompressed fluid output channel that at one end is in communication witha source of compressed fluid, and having at the other end a compressedfluid outlet orifice in communication with the internal channel of theparticle dispersion chamber.

In particular embodiments, the aerosol generating and delivery devicecomprises a plurality of directed fluid outputs, the pluralitycomprising at least one ambient air channel that at one end is incommunication with ambient air, and having at the other end an ambientair channel orifice in communication with the internal channel of theparticle dispersion chamber, the plurality further comprising at leastone compressed fluid output channel that at one end is in communicationwith a source of compressed fluid, and having at the other end acompressed fluid outlet orifice in communication with the internalchannel of the particle dispersion chamber.

In yet further embodiments, the aerosol generating and delivery devicefurther comprises a nasal adapter, oral adapter, ocular adapter, or‘vicinity’ or surface adapter (e.g., for aerosolized particle (e.g.,perfume, fragrance, essential oil or cosmeceutical agent and the like)delivery to the vicinity of a user or a target surface). in fluidcommunication with the output opening of the particle dispersionchamber.

Preferred aspects provide novel atomizer embodiments, comprising: anasal adapter; a particle dispersion chamber in communication with thenasal adapter, the dispersion chamber suitable to impart ‘vortical’ orother suitable velocity vector pattern of movement (e.g., turbulent,randomized, etc.) to particles within the internal channel of andexiting the dispersion chamber; an atomization chamber having a medicinechamber and a novel particle generating (e.g., atomization) meanscomprising a liquid feed tube and an air feed tube, the liquid feed tubein communication with the medicament in the medicine chamber, the airfeed tube in communication with a source of compressed air (e.g., an aircompressor), wherein the unique spatial relationship between output endsof the liquid and air feed tubes, and the aerodynamic particle sizefilter or ‘splitter’ element, provides a highly efficient and adjustablemeans to generate specific and suitable MMAD particle populationswithout use of a closely opposed impaction baffle and associatedexcessive medicament solution recycling and re-entrainment. According topreferred aspects, the configuration of the particle dispersion chamberfurther imparts suitable velocity vector patterns (e.g., vortical flow)to the optimally-sized particle populations for effective targeting of,for example, specific areas of the nasal cavity, olfactory region, andor paranasal sinuses via a nasal adapter.

In preferred aspects, the delivered atomized particles are comprised ofparticles substantially having a mean diameter of, for example, about 10μm to about 30 μm. Preferably, the delivered particles are comprised ofparticles substantially having a mean diameter of about 10 μm to about15 μm for targeting the olfactory region and the paranasal sinuses, andabout 15 μm to about 30 μm for targeting the overall nasal cavity.

According to further aspects, at least one of particle size or deliveryrate can be varied, and is determined by at least one variable selectedfrom several factors (in addition to the pressure and/or volume of thecompressed fluid flow) including: the internal diameter (e.g., “D1” and“D2”) and length (“L1” and “L2”) of the primary compressed fluid feedchannel 13 and primary liquid feed channel 15, respectively; the outerdiameter (“D3”) of the primary liquid feed channel 15 at the orifice 17end; the distance (“H”) from the primary orifice plane “P” (defined bythe primary compressed fluid channel orifice 7) to theplane-I-intersecting portion (as defined herein below) of the perimeterof the primary liquid feed channel end wall face 23; the angle (“A”) ofapproach between the primary liquid feed channel axis “L” and theprimary compressed fluid feed channel axis “F”; the selected distance“S” as defined herein below, the ‘offset’ distance “O” as definedherein; the internal diameter (“D4”) and length (“L4”) of the secondaryliquid feed channel 5; the distance “J” (as defined herein below)between the primary orifice plane “P” and the aerodynamic particle sizefilter member 21, and the physical characteristics of the liquid, suchas, surface tension, viscosity, density, etc. Additionally, the designand location of the particle size filtering member or ‘splitter,’ andthe design (e.g., length, taper, etc) of the particle dispersion chambercontribute to the output particle size.

Yet further embodiments provide a particle filter assembly configured tobe positioned within a stream of aerosolized particles comprising afirst group of aerosolized particles having a size greater than apredetermined size and a second group having a size less than or equalto the predetermined size, the particle filter assembly comprising: afiltering member configured aerodynamically to collect the aerosolizedparticles of the first group and to avoid collisions with theaerosolized particles of the second group permitting the aerosolizedparticles of the second group to pass thereby; and a support memberconfigured to support the filtering member within the stream ofaerosolized particles and to conduct the aerosolized particles of thefirst group collected by the filtering member to a reservoir. In certainaspects, the support member is configured aerodynamically to avoidcollisions with the aerosolized particles of the stream of aerosolizedparticles. In particular embodiments, the stream of aerosolizedparticles is produced inside an atomization chamber defined by at leastone chamber wall and the support member comprises at least one supportarm coupling the filtering member to the at least one chamber wall. Incertain aspects, the stream of aerosolized particles is produced insidean atomization chamber and emanates therefrom and the support memberpositions the filtering member outside the atomization chamber within aportion of the stream outside the atomization chamber. In someimplementations, the stream of aerosolized particles is produced insidean atomization chamber having an exit aperture through which the streammay exit the atomization chamber and the support member positions thefiltering member within the exit aperture of the atomization chamber. Inparticular aspects, the stream of aerosolized particles emanate from anaerosolization assembly comprising a liquid supply member comprising aliquid feed channel, the feed channel having an inlet in communicationwith the reservoir, an liquid supply member exit orifice, and a supplymember end-wall face having an outside diameter disposed about theliquid supply member exit orifice, the liquid supply member feed channeldefining a projected axis L, wherein the assembly further comprises acompressed fluid supply member comprising a compressed fluid channelhaving an exit orifice, wherein the end wall face liquid feed channelexit orifice are separated by a distance of at least H from compressedfluid channel exit orifice, H being measured along a projected axis Fthat is normal to a plane P defined by the compressed fluid channel exitorifice, H is equal to or greater than ¼, ½ or 1× the inner diameter D1of the compressed fluid channel adjacent the compressed fluid channelexit orifice, and Wherein the support member is configured to supportthe filtering member within the stream of aerosolized particles at adistance J from the compressed fluid channel exit orifice, J beingmeasured along the projected axis F, and wherein the distance J isgreater than the distance H.

Yet additional aspects provide a method of generating aerosol particlescomprising: directing a stream of compressed fluid into an atomizationchamber; placing a liquid feed member comprising a liquid in the streamof compressed fluid thereby disrupting a portion of the stream ofcompressed fluid; and using the disrupted portion of the stream ofcompressed fluid to atomize the liquid in the liquid feed member.Certain aspects comprise filtering particles larger than a predeterminedsize from the atomized liquid. Particular embodiments, further compriseimparting a predetermined particle flow pattern to the atomized liquid.In certain aspects, the liquid comprises at least one selected from thegroup consisting of medicaments, small or large molecule pharmaceuticalagents, liquids, solutions, suspensions, emulsions, perfumes,fragrances, essential oils, cosmeceutical agents, oils, cosmeceuticalagents, moisturizing agents, water, lotions, air fresheners, deionizingagents, aromatherapeutic agents, beverages, and skin treatments.Particular implementations, further comprise use of a nasal, ocular,oral or ‘vicinity’ adapter in communication with the atomization means.Certain aspects comprise imparting a predetermined particle flow patternto the atomized liquid and directing the atomized liquid into at leastone of a nostril of a user, both nostrils of a user, a mouth of a user,at least one of an eye of a user, and both eyes of a user. Particularaspects further comprise expelling the atomized liquid into the ambientair thereby creating a cloud of atomized liquid.

Yet further embodiments provide a method of nasal delivery ofaerosolized particles, comprising: obtaining a subject inspiring throughthe nose; delivering, over a plurality of nasal inspirations,aerosolized particles of a liquid formulation into at least one nasalpassage of the subject, wherein a volume in the range of 0.2 to 2.0 ml,0.4 to 1.5 ml, 0.6 to 1.2 ml, 0.8 to 1.1 ml, or 0.9 to 1 ml isdelivered, wherein the number of inspirations is from about 8 to about16, and wherein at least about 30%, about 50%, about 60%, about 70%,about 80% about 90% or about 100% of the delivered volume is retained inthe at least one nasal passage. In certain aspects, the average tidalvolume (V_(t)) is about 0.7 ml/Kg. In particular implementations, avolume in the range of about 0.4 to 1.5 ml, 0.6 to 1.2 ml, 0.8 to 1.1ml, or 0.9 to 1 ml is delivered.

In preferred aspects, the inventive integrated devices provideappropriately sized particle distributions having suitable dynamicoutflow properties to target specific user areas, such as in the nasalcavity or regions thereof, such as the paranasal sinuses.

The foregoing aspects and many of the attendant advantages will becomemore readily appreciated as the same become better understood byreference to the following detailed description, when taken inconjunction with the accompanying drawings. The discussion below isdescriptive, illustrative and exemplary and is not to be taken aslimiting the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B show the two dominant prior-art nebulizer designs. FIG.1A illustrates a typical internal mixing design, whereas FIG. 1Billustrates a typical external mixing design (the designs are taken fromHess, D. R., Respiratory Care, 45(6):609-622, 2000).

FIG. 2, shows, according to particular aspects of the present invention,a side cross-sectional view of an exemplary nasal atomizer embodiment,comprising: atomization means; aerodynamic particle size filteringmeans; particle dispersion chamber with plenum member; and nasaladapter.

FIG. 3, shows, according to particular aspects of the present invention,a cross-sectional view of an exemplary atomization chamber of theexemplary nasal atomizer embodiment of FIG. 2.

FIG. 4, shows, according to particular aspects of the present invention,a side cross-sectional view of the particle generating portion(atomization means) of the atomization chamber of FIG. 3. The letterdesignations “O,” “D1,” “D2,” “D3,” “D4,” “D5,” “H,” “A,” “J,” “L1,”“L2,” “L3,” and “L4” delineate particular variable aspects of theparticle generation portion that can be adjusted to alter the MMADparticle distribution.

FIGS. 5A and 5B, show, according to particular aspects of the presentinvention, a top plan view, and a side cross-sectional view,respectively, of an exemplary particle dispersion chamber andaerodynamic particle size filter means of the exemplary nasal atomizerembodiment of FIG. 2.

FIG. 6, shows, according to particular aspects of the present invention,an exploded perspective view of the exemplary particle dispersionchamber of FIG. 5, including the particle size filtering means andplenum member.

FIG. 7, shows, according to particular aspects of the present invention,a side cross sectional view of another exemplary nasal atomizerembodiment, comprising: atomization means; particle size filteringmeans; particle dispersion chamber with ambient air plenum member;compressed fluid plenum and compressed fluid outlet; and nasal adapter.

FIG. 8, shows, according to particular aspects of the present invention,a perspective view of an exemplary nasal adaptor embodiment.

FIG. 9, shows, according to particular aspects of the present invention,a perspective view of another exemplary nasal adaptor embodiment.

FIG. 10, shows, according to particular aspects of the presentinvention, a perspective view of an exemplary ocular adaptor embodiment.

FIG. 11, shows, according to particular aspects of the presentinvention, a side cross-sectional view of an exemplary ocular atomizerembodiment, comprising: atomization means; aerodynamic particle sizefiltering means; particle dispersion chamber; and ocular adapter.

FIG. 12 shows, according to particular aspects of the present invention,a side cross sectional view of yet another exemplary nasal atomizerembodiment, comprising: atomization means; aerodynamic particle sizefiltering means; and particle dispersion chamber.

FIG. 13 shows, according to particular aspects of the present invention,a side cross sectional view of yet another exemplary nasal atomizerembodiment, comprising: atomization means; atomization chamber;aerodynamic particle size filtering means; and a nasal adapter having asecond interface portion configured to be inserted into a nostril.

FIG. 14 shows, according to particular aspects of the present invention,a side cross sectional view of yet another exemplary nasal atomizerembodiment, comprising: atomization means; atomization chamber;aerodynamic particle size filtering means; particle dispersion chamber;a second intermediate compressed fluid channel, and a nasal adapterhaving an interface portion configured to be inserted into a nostril.

FIG. 15A shows, according to particular aspects of the presentinvention, an elevational perspective view of an exemplary embodiment ofa nasal adapter having a second interface portion configured to beinserted into a nostril.

FIG. 15B shows, according to particular aspects of the presentinvention, an elevational perspective view of another exemplaryembodiment of a nasal adapter configured for dual delivery and having apair of second interface portions each configured to be inserted intoone of the nostrils of a user.

FIG. 16 shows, according to particular aspects of the present invention,an elevational perspective view of another exemplary embodiment of anasal adapter having a second interface portion configured to beinserted into a nostril.

FIG. 17 shows, according to particular aspects of the present invention,an elevational perspective view of another exemplary embodiment of anasal adapter having a second interface portion configured to beinserted into a nostril.

FIG. 18 shows, according to particular aspects of the present invention,a side cross sectional view of an exemplary oral atomizer embodiment,comprising: atomization means; atomization chamber; aerodynamic particlesize filtering means; and an oral adapter.

FIG. 19 shows, according to particular aspects of the present invention,a side cross sectional view of another exemplary oral atomizerembodiment, comprising: atomization means; atomization chamber;aerodynamic particle size filtering means; particle dispersion chamber;an intermediate compressed fluid channel, and an oral adapter.

FIG. 20 shows, according to particular aspects of the present invention,an elevational perspective view of an exemplary embodiment of an oraladapter having a mouthpiece configured to be inserted into the mouth ofa user. Such laterally deflecting embodiments also serve as vicinityadapters for delivery of aerosolized particles to the vicinity of a useror to desired target surfaces (e.g., for delivery of perfume, fragrance,essential oil or cosmeceutical agent and the like).

FIG. 21 shows, according to particular aspects of the present invention,an elevational perspective view of an exemplary embodiment of an oraladapter having a mouthpiece configured to be inserted into the mouth ofa user. Such laterally deflecting embodiments also serve as vicinityadapters for delivery of aerosolized particles to the vicinity of a useror to target surfaces (e.g., for delivery of perfume, fragrance,essential oil or cosmeceutical agent and the like).

FIG. 22 shows, according to particular aspects of the present invention,a side view of another exemplary embodiment of a dispersion chamberand/or a delivery adapter (e.g., a dispersion chamber and/or a vicinityadapter for delivery of aerosolized particles to the vicinity of a useror to desired target surfaces (e.g., for delivery of perfume, fragrance,essential oil or cosmeceutical agent and the like)).

FIG. 23 shows, according to particular aspects of the present invention,a side cross-sectional view of an additional exemplary atomizerembodiment, comprising: atomization means; particle dispersion chamberand/or vicinity adapter; and angled removable (e.g., modular) liquidholding container with upper and lower apertures for liquid return andliquid entrainment, respectively.

FIG. 24 shows a side elevational exploded sectional view of theexemplary embodiment of FIG. 23.

FIG. 25 shows, according to particular aspects of the present invention,a side cross-sectional view of an additional exemplary atomizerembodiment, comprising: atomization means; particle dispersion chamberand/or vicinity adapter; removable internal container, and externalmodular liquid holding container.

FIG. 26 shows a side elevational exploded sectional view of theexemplary embodiment of FIG. 25.

DETAILED DESCRIPTION OF THE INVENTION

Aspects of the present invention include aerosol generating and relateddelivery devices, such as atomizers and nebulizers. Further aspectsinclude a filter member configured for use with such devices. Additionalaspects include integrated atomizer and particle dispersion chamberapparatuses. The technology disclosed herein may have medicalapplications as well as non-medical applications. Further, variousadapters may be used to configure the technology to deliver aerosolizedparticles to specific areas of the human body as well as to configurethe technology for specific purposes (e.g., delivery of aerosolizedparticles to the vicinity of a user or to a target surface).

With respect to exemplary medical uses, prior art topical drug deliverymethods are ineffective at penetrating very far into the nasal cavityand not at all into the paranasal sinuses. This is a significantlimitation/problem, because systemic delivery via inhalation utilizingthe nasal mucosa and mucosa in the paranasal sinuses is highly desirablefor many targeted disease states.

Preferred aspects of the present invention provide novel atomizers, andnovel integrated atomizers and particle dispersion chamber apparatusesthat have the ability to deliver medicaments (e.g., such as the drugspresently prescribed for many diseases and conditions) as doses of verytiny medicine-containing particles over a broad particle range, and withmedicament having significant viscosity. Inventive effective deliveryis, for example, by using a nasal adapter that, in combination with theinventive particle generation and dispersion aspects, allows moreefficacious topical and systemic targeted delivery within the nasalcavity and regions thereof of a user. Alternatively, effective inventivedelivery may be by an ocular adaptor, oral adapter, vicinity adapter andthe like.

Examples of diseases and/or conditions that can be treated by medicamentdelivery using the inventive apparatus and methods include, but are notlimited to, endocrine and metabolic disorders, sinusitis, infection,migraines, sleep disorders, autoimmune diseases, osteoporosis,neurological diseases and disorders, obesity, sexual dysfunctions,diabetes, cardiovascular diseases and episodes, respiratory diseases,cystic fibrosis, cancer, ocular diseases and/or conditions including,but not limited to allergies, conjunctivitis, corneal infections, dryeye, Fuchs' Dystrophy, and others. Any of the aforementioned diseasesand/or conditions that require systemic delivery of medications couldalso be treated through the mouth. The inventive devices can also beused for aerosolized antigen-mediated immunization, vaccination, etc.

According to preferred aspects, the particle size (e.g., MMAD particledistribution), particle dispersion technology (e.g., velocity vectorpattern), and duration of application allow the medicine to reach andpermeate the targeted area of the nasal cavity, and thus enableeffective systemic delivery of medicament via the nasal cavity, eye,cheeks, and the like. For example, essentially any and all medicinescurrently applied (e.g., by direct action) to the nasal cavity andparanasal sinuses, including relatively viscous medicines and solutions,can be used or adapted (e.g., formulated) for use with the inventiveatomizer and/or integrated atomizer embodiments, including but notlimited to over-the-counter nasal medicines (e.g., for allergy and coldsand flu) and prescription medicines.

Similarly, essentially any and all medicines currently applied (e.g., bydirect action) to the surface of the eye, can be used or adapted (e.g.,formulated) for use with the inventive atomizer and/or integratedatomizer embodiments, including but not limited to over-the-counterocular medicines (e.g., for allergies and eye irritation) andprescription medicines. Further, essentially any and all medicinescurrently applied (e.g., by direct action) to the inside of the mouth(e.g., the inside of the cheeks), can be used or adapted (e.g.,formulated) for use with the inventive atomizer and/or integratedatomizer embodiments, including but not limited to over-the-counternasal or oral medicines (e.g., for allergies and sores) and prescriptionmedicines. Additionally, medicines currently delivered/taken orally, byskin patch, or parenterally can be adapted (e.g., formulated) fordelivery use using the inventive atomizer and integrated atomizerembodiments. In particular embodiments, the technology disclosed hereinmay be used to generate a cloud or fog of atomized particles or dropletsthat may be exposed to the skin. Following exposure, one or moreliquids, such as a liquid solvent, included in the atomized particles ordroplets may dry leaving materials (e.g., medicines, perfume, fragrance,essential oil or cosmeceutical agents, lotions, and the like) behind onthe skin, which may remain on the surface of the skin or be absorbedthereby. Alternatively, the user's skin may absorb one or more of theliquids included in the atomized particles or droplets.

Among the many enabled utilities, the instant devices can be used fordelivery of drugs to the brain to treat conditions of the centralnervous system (CNS); so-called ‘Nose-to-Brain’ delivery. In thisprocess, drugs delivered to the olfactory region of the nasal cavity(e.g., delivered very high through small passages) can enter the brainand bypass the so-called blood brain barrier. This inventive utilityprovides a very significant, here-to-fore unavailable method of drugdelivery. Significantly, to achieve nose-to-brain delivery, the deliverydevice must be capable of efficiently providing a dynamic particlepopulation suitable to target and reach this area. Significantly,according to preferred aspects, the inventive integrated atomizer hassubstantial utility for both topical and systemic delivery of drugs,therapeutics, and other beneficial compounds, and provides fornose-to-brain delivery of drugs, therapeutics and other beneficialcompounds.

In particular aspects, and for a user with a secondary condition ofnasal polyps, the inventive apparatus and methods allow far moreeffective application of medicine, which is otherwise blocked orprecluded by such secondary conditions using contemporary systems. Forexample, prior art nasal inhalers and spray bottles are used to delivercorticosteroids, which, at least in theory, is designed to slowre-growth of polyps subsequent to polyp removal. Currently, however,such devices are largely ineffective at accomplishing this, often notslowing polyp growth at all. According to preferred aspects, theinventive apparatus and methods described herein provide forsubstantially improved and more effective slowing of such polypre-growth.

According to additional aspects, many of the side effects of particularmedicine delivery are precluded or eradicated by the inventive devicesand methods. With many sprays, for example, the propellant causes adrying of the nasal passages leading to bleeds. Therefore, with suchapplications, a secondary spray of saline is added to the treatment inan attempt to control such bleeding. Additionally, for example, steroidsin pill form have many unpleasant side effects such as internalbleeding, a redistribution of fluid to the head, neck and back causingunsightly “humps,” and easy bruising, to name a few. An effective use ofthe inventive integrated atomizer for such steroid delivery does nothave these attendant pill-based side effects.

Current nasal drug delivery devices deliver droplets in a range from 50μm to 100 μm. Significantly, due to the size of the droplets and thephysical characteristics of the nasal cavity, the maximum dose that canbe delivered is 200 μl per nostril. This limitation on the deliverableamount of medicament volume (e.g., mass) restricts the formulationcharacteristics and limits additives that could assist in achieving thegoals of the medication. By contrast, because of its unique and novelconfiguration, the inventive atomizer generates droplets that are muchsmaller, and substantially more suitable for deposition on a much largersurface area of the nasal cavity, particularly when an inventiveintegrated atomizer is used. The inventive atomizer, therefore, candeliver doses up to 2 ml to the nasal cavity, thus allowing for use ofoptimal/superior formulations and effectiveness.

The inventive devices could also be used to deliver aromatherapy. Forexample, the inventive apparatuses could be used to expel aerosolizedparticles into the air (e.g., in the vicinity of the user). Theseparticles are then be perceived by the user located an appropriatedistance from the device for an appropriate amount of time to receive atherapeutically significant quantity of aerosolized particles.

Non-medical uses include the aerosolization of perfume, fragrance,essential oil or cosmeceutical agents and the like. By way of example,the inventive apparatuses could be used to expel a cloud of aerosolizedparticles into the air through which the user to could pass his/herskin, clothes, and/or hair, thereby allowing a portion of theaerosolized particles to settle thereupon. Alternatively, the devicescould be used to target surfaces with such aerosolized particles.Flavored particles could be delivered (e.g., to the tongue or nasalcavity, or to other surfaces). Adhesives could be delivered. Paintscould be delivered.

Overview

With reference to FIGS. 2-4 and the definitions provided below, anoverview of aspects of the present invention will now be described. Anexemplary embodiment of an atomizer 1 configured for nasal delivery ofaerosolized particles is shown in FIG. 2. The atomizer 1 includes anatomization housing 2 defining an atomization chamber 4 in communicationwith, or comprising holding means (e.g., a reservoir portion 6) suitablefor holding a liquid (e.g., medicament solution), which can be filled toone or another suitable level (e.g., consistent with the configuration,and desired dosage, etc.) identified or marked by reference numeral 9(FIG. 3).

The atomizer 1 may include an atomization means 11 housed inside theatomization housing 2. The atomization means 11 includes a primaryliquid feed channel 15 in communication with the liquid held in theholding means. The primary liquid feed channel 15 may receive the liquidfrom a secondary liquid feed channel 5 that is in fluid communicationwith the holding means (e.g., the reservoir portion 6). In other words,the secondary liquid feed channel 5 is intermediate between the primaryliquid feed channel 15 and the holding means.

The atomization means 11 may be optionally driven by a compressed fluidsource (not shown), inhalation, and the like. For convenience ofillustration, the compressed fluid driven embodiments will describedfirst. In such embodiments, the atomization means 11 includes a primarycompressed fluid channel 13 in communication with an external orinternal compressed fluid source (not shown). As may best be viewed inFIG. 4, the primary compressed fluid channel 13 has a correspondingorifice 7 defining a projectable longitudinal compressed fluid feedchannel axis “F,” in operative communication with the primary liquidfeed channel 15 and its corresponding orifice 17. The primary compressedfluid channel 13 receives compressed fluid from a secondary compressedfluid channel 8 in fluid communication with the compressed fluid source(not shown). In other words, the secondary compressed fluid channel 8 isintermediate between the primary compressed fluid channel 13 and asource of compressed fluid. The atomization means 11 is suitablyconfigured to entrain a liquid in a fluid flow stream (not shown) togenerate a particle (e.g., aerosolized liquid droplet) flow along (e.g.,centered along) the projected axis “F.”

In embodiments driven by inhalation, the secondary compressed fluidchannel 8 may be open to the ambient air and inhalation by the user maydraw ambient air into the secondary compressed fluid channel 8 and theprimary compressed fluid channel 13 couple thereto. In such embodiments,the “compressed fluid” in the primary compressed fluid channel 13 mayinclude air drawn into the device by the user's inhalation.

Returning to FIG. 2, the atomizer 1 may include an aerodynamicparticle-size filtering means or filtering member 21 (e.g., air-foilmember) suitably configured and positioned at a distance “J” from theprimary orifice plane “P” (defined by the primary compressed fluidorifice 7 in a manner explained below) to direct fluid flow around itscontour, and thereby non-collisionally redirect particle flow of thedesired particle size range around its contour, while simultaneouslyblocking larger particles for return to the liquid reservoir andre-entrainment. In other words, the filtering member 21 separatesparticles having a size larger than a predetermined size from particleshaving a size less than or equal to the predetermined size. Theparticles having a size larger than the predetermined size are collectedby the filtering member 21 and returned to the holding means. Theparticles having a size less than or equal to the predetermined sizepass by the filtering member 21.

Optionally, the atomizer 1 may include a particle dispersion chamber 10having an optional dispersion chamber outer housing 28, an optionalintermediate compressed fluid channel 40, various connector componentsused to couple these components to the atomization chamber 4, and thelike. The dispersion chamber outer housing 28 may be optionally fittedwith a nasal adapter 42 (see FIGS. 2 and 7-9), a nasal adapter 60 (seeFIGS. 13-17), an ocular adapter 48 (see FIGS. 10 and 11), an oraladapter (see FIGS. 18-21), and the like. As is apparent to those ofordinary skill, atomizers and nebulizers may be configured for use withvarious accessories, adapters, and the like and the invention is notlimited to use with any particular accessories, adapters, and the like.

DEFINITIONS

The term “liquid,” as used herein with respect to a liquid to beatomized using the inventive devices and methods, refers to any liquidor solution, including medicament solutions and drug or agentformulations and solutions. Liquid also encompasses liquids andsolutions of various viscosities.

The terms “particle filter,” “particle size filter” (e.g.,aerodynamically particle size filtering means), and “splitting means,”as used herein, refer to a particle filter (e.g., an aerodynamicparticle size filtering member) suitably configured and positioned atthe distance “J” from the primary compressed fluid orifice 7 (e.g., froma primary orifice plane “P”, as defined herein) to provide anaerodynamic fluid flow around the surface. Preferably, the particlefilter, and/or the configuration and placement thereof, provides for aproportion of atomized particles that collide with the member and aproportion of non-colliding particles with velocity vectors that avoidthe surface and/or are carried in the aerodynamic fluid flow around thesurface.

The term “holding means” as used herein, refers to a liquid or solutionreservoir (e.g., the reservoir portion 6) for holding the liquid orsolution to be atomized. Liquid or solution in the holding means is incommunication with the atomization means 11 via one or more liquid feedchannels (e.g., the secondary liquid feed channel 5). In preferredembodiments, the holding means is configured so that impaction liquidfrom the inventive filtering member 21 is returnable to the holdingmeans for re-entrainment by the atomization means 11. The holding meanscan be of any suitable configuration, and, for example, can beconfigured as part of the atomization chamber 4 per se, or alternativelycan be a holding means (e.g., a cartridge, vial or other liquid,solution or medicament container) that is insertable into theatomization chamber 4 so that a liquid, solution or medicament containedtherein is in communication with the atomization means 11.

The term “primary orifice plane ‘P’” as used herein with respect toparticular exemplary embodiments, refers to a positional reference planenormal to the projectable longitudinal compressed fluid feed channelaxis “F”, definable by the configuration and contour of a perimeter 7A(e.g., circular perimeter, or otherwise) of the primary compressed fluidorifice 7. As shown in the exemplary embodiments described herein, theperimeter 7A of the primary compressed fluid orifice 7 defines a normal,horizontal surface, for which the reference primary orifice plane “P”provide direct reference (e.g., for purposes of describing the distanceof a filtering member 21 or other element along the axis “F”). It shouldbe understood, however, that the precise shape of the perimeter 7A ofthe primary compressed fluid orifice 7 may be other than the exemplaryregular, normal or horizontal shape and may assume a variety of suitableconfigurations, and in such cases the positional reference plane (i.e.,the primary orifice plane “P”) will still be normal to the projectablelongitudinal compressed fluid feed channel axis “F”, but will bepositioned along the axis “F” at the median position along axis “F” ofthe primary compressed fluid orifice 7, regardless of the regularity,shape, slope, configuration, etc., thereof. For example, if the primarycompressed fluid orifice 7 is circular, but is angled (slopped) ratherthan normal to the axis “F”, then primary orifice plane “P” will be aplane “P” positioned normal to axis “F”, but at a position along axis“F” corresponding to the center point of the primary compressed fluidorifice 7. In this manner, the primary orifice plane “P” serves itsreference position function with respect to defining a distance to otherelements of the inventive devices.

The term “channel end-wall face” as used herein with respect toparticular exemplary embodiments, refers to a positional reference planedefinable by the configuration and contour of a perimeter 17A of theprimary liquid feed channel orifice 17 and the configuration and contourof an end-wall face 23 of the primary liquid feed channel 15. Theend-wall face 23 having a perimeter 23A. As shown in particularexemplary preferred embodiments described herein, the perimeter 17A ofthe primary liquid feed channel orifice 17 and the perimeter 23A of theend-wall face 23 define a surface 17C that is normal to a liquid feedchannel axis “L,” and that is disposed at an acute angle “A” withrespect to the axis “F.” It should be understood, however, that theprecise shape of the perimeter 17A of the primary compressed fluidorifice 17 and/or the perimeter 23A of the end-wall face 23 may be otherthan the exemplary regular, normal or horizontal or angled shape and mayassume a variety of suitable configurations, and in such cases theend-wall face 23, regular or irregular, may be other that normal to theprojectable longitudinal liquid feed channel axis “L”. For example, ifthe primary liquid feed channel orifice 17 and end-wall face 23 iscircular, but is but is horizontal (e.g., normal with respect to theaxis “F”), then the orifice 17 and end wall face 23 (or a planerepresenting the average configuration/shape of the orifice and end-wallface) will be normal to axis “F”, but at an angel with respect to axis“L”. Therefore, a variety of suitable shapes and configurations of theprimary compressed fluid orifice 17 and/or the end-wall face 23 areencompassed by the present invention, and these may be disposed atvarious angels with respect to the axis “F.” Therefore, for purposes ofthe present invention, the positioning, with respect to the projectableaxis “F”, of the end-wall face 23 and orifice 17 thereof are defined bythe positioning, normal to axis “F,” of a closest plane “I”-intersectingportion 23B of the perimeter 23A of the end-wall face 23, where plane“I” is a plane defined by the intersection of the axis “F” with the axis“L”. In this manner, the distance of the perimeter 23A of the end-wallface 23 from the axis “F” can be defined, regardless of the shape,configuration, or orientation of the end-wall face 23 and the primaryliquid feed channel orifice 17 thereof.

Atomization Means 11

As mentioned above, the atomization housing 2 houses the atomizationmeans 11 and defines an atomization chamber 4 in communication with, orcomprising holding means. Alternatively, the atomization means 11 mayinclude a housing 2A having a wall 2C defining the atomization chamber 4in which the liquid or solution is atomizable. In the embodimentdepicted in FIG. 2, the atomization chamber 4 includes a reservoirportion 6 that serves as the holding means suitable for holding a liquidor solution to be atomized.

With reference to FIGS. 2, 3, and 4, to allow for compressedfluid-driven (e.g., compressed air-driven) particle generation, theatomization chamber 4 is in communication with the compressed fluidsource (e.g., an air compressor, tank, compressed gas cartridge, and thelike) via the primary compressed fluid orifice 7, the primary compressedfluid feed channel 13, and, in certain embodiments, a secondarycompressed fluid channel 8 that communicates between the primarycompressed fluid feed channel 13 and the source of compressed fluid. Theprimary compressed fluid orifice 7 is located at a first end 13A of theprimary compressed fluid feed channel 13, is in fluid communication withthe atomization chamber 4, and defines the primary orifice plane “P.” Asecond open end 13B opposite the first end 13A of the channel 13 is influid communication with the compressed fluid source (e.g., an aircompressor), which may, in certain embodiments, may be via the secondarycompressed fluid channel 8. The channel 13 and/or orifice 7 define theprojectable compressed fluid feed channel axis “F.”

The primary compressed fluid feed channel 13 (e.g., cylinder, tube,channel, bore, etc.) has a length “L1,” an inner diameter “D1.” Thesecondary compressed fluid channel 8 has an inner diameter “D5” and alength “L4” (see FIG. 3). In the embodiment depicted in the drawings,the secondary compressed fluid channel 8 has a first portion 8A coupledto the channel 13 and a second larger diameter portion 8B coupledbetween the first portion 8A and the compressed fluid source (notshown). In the embodiment depicted in FIG. 2, compressed fluid issupplied to the atomization chamber 4 via a channel having threesegments of decreasing inner diameter (i.e., the second portion 8B, thefirst portion 8A, and the primary compressed fluid channel 13). However,as is apparent to those of ordinary skill in the art, embodiments inwhich the inner diameter “D5” of the first portion 8A is greater than orsubstantially equal to the inner diameter of the second portion 8B arealso within the scope of the present invention.

As may best be viewed in FIG. 4, the primary liquid feed channel 15(e.g., cylinder, tube, channel, bore, etc.) has a length “L2,” an innerdiameter “D2,” a channel wall 19, and a channel end-wall face 23 at afirst end 15A. The channel 15 also includes an outside diameter “D3”disposed about (e.g., radially about) the primary liquid feed channelorifice 17 in fluid communication with the atomization chamber 4. Theprimary liquid feed channel 15 has a second end 15B in optionalcommunication with a secondary liquid feed channel 5 having a length“L3” (see FIG. 3) and an inner diameter “D4.” The secondary liquid feedchannel 5 is in communication with the liquid holding means 6. Theprimary liquid feed channel 15 defines a projectable longitudinal liquidfeed channel axis “L.”

According to preferred aspects, the inventive, highly efficientatomization means 11 is uniquely configured such that: (a) the channelend wall face 23 with the liquid feed channel orifice 17 is separated byat least a distance “H” (e.g., vertical distance or height, in the caseof vertically oriented embodiments) from the a primary orifice plane“P,” the distance “H” being measured along the projected longitudinalaxis “F”; and (b) the longitudinal axis “L” intersects the longitudinalaxis “F” at the acute angle “A.” In preferred embodiments, and at thedistance “H” along the axis “F,” the plane “I”-intersecting portion 23Bof the perimeter 23A of the end wall face 23 is positioned within aselected distance “S” from axis “F” (measured perpendicular to the axis“F”) and this distance is sometimes referred to herein as the offsetdistance “O.”

In some embodiments, the selected distance “S” is such that there is‘overlap’ of axis “F” with the plane “I”-intersecting portion 23B of theperimeter 23A of the end wall face 23, where, as used herein, there is‘overlap,’ if the projected axis “F” intersects the end wall face 23 orthe liquid feed channel orifice 17 thereof. In such overlappingembodiments the selected distance “S” is sometimes referred to herein asa negative offset “minus O” distance. When there is negative offset(i.e., a minus O distance), the orifice 7 is positioned adjacent to adiverting portion 19A of the wall 19 of the primary liquid feed channel15 aligning at least a portion of the flow of compressed fluid alongaxis “F” with the diverting portion 19A of the wall 19 and causing afirst portion of the compressed fluid to strike (or impact) thediverting portion 19A of the wall 19. A portion of the compressed fluidis also directed around the outside of the diverting portion 19A of thewall 19. Without being limited by theory, directing the flow ofcompressed fluid around the diverting portion 19A may disrupt or spreadthe column of compressed fluid leaving the orifice 7. Therefore, unlikeprior art or conventional atomizers and nebulizers that avoid spreadingor disrupting the flow of compressed fluid before it strikes theimpactor thereby maximizing the portion of the flow of atomizedparticles that strike the impactor, certain embodiments of the presentinvention spread the flow of compressed fluid before it engages theliquid to be atomized.

In various embodiments, outside of the diverting portion 19A of the wall19 may be contoured. As the compressed fluid traverses the contouredsurface, the velocity of the fluid is increased and pressure around thediverting portion 19A of the wall 19 may decrease to below that of theuninterrupted flow of compressed fluid. In the embodiment depicted inFIG. 4, the orifice 7, channel 15, and wall 19 thereof are arranged suchat the orifice 7 extends substantially between the portion 23B of theperimeter 23A of the channel end face 23 and the center of the channel15 along plane “P.” In this embodiment, the compressed fluid will betraveling at different rates along the diverting portion 19A in theaxial direction of axis “F.”Specifically, the fluid will be travelingfaster near the center of the orifice 7 than near the portion 23B of theperimeter 23A of the end wall face 23 where it traverses a smallerportion of the diverting portion 19A.

In other embodiments, the selected distance “S” is such that there is no‘overlap’ of axis “F” with the plane “I”-intersecting portion 23B of theperimeter 23A of the end wall face 23 (i.e., the projected axis “F” doesnot intersect the end wall face 23 or the liquid feed channel orifice 17thereof). In such non-overlapping embodiments, the selected distance “S”is sometimes referred to herein as a positive offset “plus O” distance.

In particular embodiments, the selected distance “S” from projected axis“F” is less than or equal to ½×D1, and in instances where there is nooverlap as defined herein, this distance would correspond to a “plus O”value that is less than or equal to ½×D1. In alternate embodiments, theselected distance “S” from projected axis “F” is less than or equal to½×D1, and in instances where there is overlap as defined herein, thisdistance would correspond to a “minus O” value that is less than orequal to ½×D1 (see, e.g., “O” in FIG. 4). In particular embodiments,offset distance “O” (plus or minus) is less, equal to or greater than½×D1. In particular embodiments, offset distance “O” (plus or minus) isless than ½×D1, and preferably “minus O” is less than ½×D1. Inparticular embodiments, neither the plane-I-intersecting portion 23B ofthe perimeter 23A of the end wall face 23 nor a plane-I-intersectingportion 17B of the perimeter 17A of the liquid feed channel orifice 17overlap projected axis “F.” In other embodiments, theplane-I-intersecting portion 23B of the perimeter 23A of the end wallface 23 overlaps projected axis “F,” whereas the plane-I-intersectingportion 17B of the perimeter 17A of the liquid feed channel orifice 17does not. In yet additional embodiments, both the plane-I-intersectingportion 23B of the perimeter 23A of the end wall face 23 and theplane-I-intersecting portion 17B of the perimeter 17A of the liquid feedchannel orifice 17 overlap projected axis “F” (i.e., the projected axis“F” intersects the liquid feed channel orifice 17 of the end wall face23).

It will be appreciated by those of skill in the art that the preciseshape of the primary compressed fluid orifice 7 and/or the primaryliquid feed orifice 17 may vary (e.g., circular, ovoid, rectangular,square, etc.), and that the present inventive aspects encompass suchvariations, and that the shapes may be regular (e.g., flat, smooth,gently curved) or irregular (jagged, abruptly curved, rough, etc.).Additionally, it will be appreciated by those of skill in the art thatthe precise angular disposition of the primary compressed fluid orifice7 and/or the primary liquid feed orifice 17 with respect to the axis “F”and axis “L”, respectively, may vary (e.g., normal, acute, obtuse), andthat the present inventive aspects encompass such variations.

In particular embodiments, distance “H” is less than diameter “D1,”equal to diameter “D1,” or greater than diameter “D1.” In particularembodiments, distance “H” is greater than diameter “D1.” Preferably,distance “H” is equal to or greater than diameter “D1.”

In some embodiments, distance “H” is less than diameter “D2,” equal todiameter “D2,” or greater than diameter “D2.” In some embodiments,distance “H” is greater than diameter “D2.” Preferably, distance “H” isequal to or greater than diameter “D2.”

In particular embodiments, distance “H” is less than diameter “D3,”equal to diameter “D3,” or greater than diameter “D3.” In someembodiments, distance “H” is less than diameter “D3.” Preferably,distance “H” is equal to or less than diameter “D3.”

In some embodiments, distance “H” is less than diameter “D3,” butgreater than diameter “D1,” or distance “H” is less than diameter “D3,”but greater than diameter “D2.” In some embodiments, diameter “D2” isequal to or greater than diameter “D1.” In some embodiments, thedistance “H” is equal to or greater than ¼, ½ or 1× the inner diameter“D1” of the primary compressed fluid feed channel 13. In particularaspects, distance “H” is less than diameter “D3,” and greater than bothdiameter “D1” and diameter “D2.” In some embodiments, distance “H” isgreater than any one of diameter “D1,” diameter “D2,” and diameter “D3.”

In particular embodiments, the atomization means 11 is configured suchthat, during operation of the atomization device 1, the longitudinalprimary fluid feed channel axis “F” of the primary compressed fluid feedchannel 13 is vertically oriented, or substantially vertical (e.g.,within 5 or 10 degrees of vertical), within the atomization chamber 4.

In particular embodiments, the diameter “D1” of the primary orifice 7 isfrom about 0.1 mm to about 1 mm, about 0.2 mm to about 0.6 mm, about0.25 mm to about 0.4 mm, or preferably about 0.29 mm to about 0.46 mm.

In particular embodiments, the diameter “D2” of the primary liquid feedchannel orifice 17 is from about 0.15 mm to about 1.5 mm, about 0.25 mmto about 1.0 mm, about 0.3 mm to about 0.75 mm, or preferably about 0.38mm to about 0.50 mm.

In particular embodiments, the outer diameter “D3” of the primary liquidfeed channel end wall face 23 is from about 0.2 mm to about 4.0 mm,about 0.4 mm to about 3.0 mm, about 0.6 mm to about 2.5 mm, orpreferably about 0.76 mm to about 2.03 mm.

In other embodiments, diameter “D4” is from about 2 mm to about 2.5 mm.In various embodiments, the inner diameter “D4” is larger than the innerdiameter “D2” of the primary liquid feed channel. In particular aspects,diameter “D4” is greater than or equal to 2×D2, 3×D2, 4×D2, 5×D2, 10×D2,15×D2, 20×D2, 30×D2, 40×D2 or 50×D2. In particular embodiments, ininside diameter “D4” of the secondary liquid feed channel 5 is fromabout 1.5 mm to about 4 mm, about 1.5 mm to about 3 mm, or about 1.5 mmto about 2.5 mm. In some aspects, diameter “D4” is from about 1 mm toabout 5 mm, from about 1.5 mm to about 3 mm, or from about 2 mm to about2.5 mm. In such preferred embodiments, the relatively large diameter“D4” (i.e., relative to prior art atomization and nebulization deviceswhich have relatively narrow liquid channels) enables atomization anddelivery of relatively viscous liquids (e.g., 5-105 centipoise) andsolutions that cannot be effectively atomized, nebulized or delivered bydevices of the prior art (which cannot effectively atomize, nebulize ordeliver particles greater than about 5 centipoise). According topreferred aspects, diameter “D4” is greater than the diameter ofcorresponding primary and secondary liquid feed channels of conventionalprior art atomizers and nebulizers, thereby reducing the liquid flowresistance relative to prior art devices, and allowing for effectiveatomization and delivery of liquids of substantially increased viscosityrelative to those liquids effectively atomizable or nebulizable by priorart devices. This also facilitates a higher rate of delivery (more massdelivered per unit time, relative to prior art devices). In particularembodiments, the distance “H” from the primary orifice plane “P” rangesfrom about 0.02 mm to about 5.0 mm, about 0.1 mm to about 5.0 mm, about0.15 mm to about 4.0 mm, about 0.2 mm to about 3.0 mm, or preferablyabout 0.25 mm to about 2.03 mm.

In particular embodiments, the selected distance “S” or the offsetdistance “O” (plus or minus) from longitudinal axis “F” is less than,equal to, or greater than ½×D1. Preferably, selected distance “S” oroffset distance “O” (plus or minus) is less than or equal to ½×D1. Morepreferably, selected distance “S” or offset distance “O” (plus or minus)is less than ½×D1. The selected distance “S” may be equal to or lessthan twice the inner diameter “D1” of the primary compressed fluid feedchannel 13.

In particular embodiments, the angle “A” is between about 30 degrees andabout 70 degrees, between about 45 degrees and about 70 degrees, orbetween about 55 degrees and about 65 degrees. In some embodiments, theangle “A” is about 55 degrees.

In particular embodiments, the distance “J” from the primary orificeplane “P” ranges from about 0.1 mm to about 40 mm, 0.1 mm to about 25mm, 0.1 mm to about 5.0 mm, about 0.15 mm to about 4.0 mm, about 0.2 mmto about 3.0 mm, or preferably about 0.25 mm to about 2.0 mm.

Dispersion Chamber 10

The linear atomizer embodiment 1 of FIG. 2 additionally comprises aparticle dispersion chamber 10 in fluid communication with theatomization means 11 of the atomization chamber 4. The particledispersion chamber 10 imparts a velocity vector or flow pattern (e.g.,‘vortical,’ randomized, turbulent, etc. flow) to the aerosolizedparticles (e.g., atomized particles) received within and exiting fromthe particle dispersion chamber 10. Additionally, the particledispersion chamber 10 serves to define further the particle size afterthe droplets are created by and received from the atomization means 11.

The particle dispersion chamber 10 comprises a housing 16 having a wall16A, an atomization chamber-proximal input opening 16B, an atomizationchamber-distal output opening 16C, and an internal particle dispersionchannel 22 communicating between the input opening 16B and the outputopening 16C. The input opening 16B is in fluid communication with theatomization chamber 4 and the particle dispersion chamber 10 isconfigured to operatively receive atomized particles therethrough fromthe atomization means 11. The atomization chamber 4 includes an openportion 4A through which atomized particles may exit the atomizationchamber 4 and the particle dispersion chamber 10 includes an atomizationchamber-proximal input opening 16B through which atomized particles mayenter the particle dispersion chamber 10.

In the embodiments depicted in FIGS. 2, 7, and 11, the input opening 16Bof the particle dispersion chamber 10 is coupled directly to the openportion 4A of the atomization chamber 4 to allow the passage of atomizedparticles from the atomization chamber 4 to the particle dispersionchamber 10. For example, the open portion 4A may be formed in the top ofthe atomization chamber 4 and the particle dispersion chamber 10attached to the top of the atomization chamber 4 with its input opening16B juxtaposed with the open portion 4A of the atomization chamber 4.

In alternate embodiments depicted in FIGS. 12, 14, and 19, a connectoror collar “C1” is disposed between the particle dispersion chamber 10and the atomization chamber 4. The collar “C1” may include a recessedportion “R1” configured to receive a portion of the particle dispersionchamber 10 and position the input opening 16B of the particle dispersionchamber 10 adjacent to the open portion 4A formed in the top of theatomization chamber 4.

The particle dispersion chamber 10 may additionally include, orcommunicate with, an aerodynamic particle size filtering member,‘splitter’ member, or filtering member 21, suitably configured andpositioned at a distance from the primary orifice plane “P” (defined bythe primary compressed fluid orifice 7) to non-collisionally redirectflow of the desired particle size range around its contour whilesimultaneously blocking larger particles for return to the liquidreservoir and re-entrainment. In other words, the filtering member 21separates particles having a size larger than a predetermined size fromparticles having a size less than or equal to the predetermined size.The particles having a size larger than the predetermined size arecollected by the filtering member 21 and returned to the holding means.The particles having a size less than or equal to the predetermined sizepass by the filtering member 21.

In the embodiments depicted in the figures, the filtering member 21 isdisposed between the input opening 16B of particle dispersion chamber 10and the open portion 4A of the atomization chamber 4. In this manner,the filtering member 21 selectively filters particles larger than apredetermined size from the particle stream preventing them fromentering the particle dispersion chamber 10 and returning them to theholding means to be re-aerosolized.

An upper portion of the wall 2A defining the atomization chamber 4 mayinclude a lip 2B configured to receive and support the filtering member21 adjacent the open portion 4A. In the embodiments depicted in FIGS. 2,5B, 6, 7, and 11, a lower portion of the wall 16A located in theinterior of the chamber 10 may include a recessed portion 16D configuredto receive a portion of the filtering member 21 and rest thereupon. Inalternate embodiments depicted in FIGS. 12, 14, and 19, the collar “C1”includes a recessed portion “R2” configured to receive a portion of thefiltering member 21 and rest thereupon.

Preferably, the internal channel 22 of the chamber 10 is configured soas to sustain, and not disrupt, the particle flow or dispersion patterngenerated therein and exiting therefrom through the output opening 16C.Preferably, therefore, the internal channel 22 is, for example,cylindrical or substantially cylindrical (e.g., slightly tapered),smooth tapered cylindrical, etc., such that there are no abruptdiscontinuities along the internal surface thereof, or surfacestructures or elements extending within the internal channel 22, or endcaps, restrictions or elements that restrict the output opening 16C ofthe channel 22, that would disrupt the flow pattern imparted to theparticles within the internal channel 22 and exiting the output opening16C thereof.

The particle dispersion chamber 10 additionally comprises one or moredirected fluid channels (e.g., 18 or 24) within the wall 16A suitable,in operation, to impart a desired velocity vector flow pattern (e.g.,‘vortical,’ randomized, turbulent, etc., flow) to aerosolized particleswithin and exiting the internal channel 22 through its output opening16C. In particular embodiments, such as those shown in FIGS. 1-6, thewall 16A of the particle dispersion chamber 10 comprises at least oneambient air channel 24 having a first ambient air channel orifice 26Acommunicating with the internal channel 22 of the particle dispersionchamber 10 and a second ambient air channel orifice 26B in communicationwith ambient air. In particular embodiments, the at least one ambientair channel 24 and ambient air channel orifice 26A is configured withinthe wall 16A to operatively direct ambient air (e.g., during userinhalation) tangentially with respect the longitudinal axis of theinternal channel 22 of the particle dispersion chamber. In otherembodiments, the at least one ambient air channel 24 and ambient airchannel orifice 26A are configured within the wall 16A to operativelydirect ambient air (e.g., during user inhalation) tangentially and at anacute forward angle with respect a longitudinal axis of the internalchannel 22 of the particle dispersion chamber 10; that is, preferably,the ambient air flow vector from the ambient air channel orifice 26A isdirected tangentially with respect to the internal channel 22configuration, and the flow vector has both radial and longitudinalcomponents with respect to the internal channel 22 axis, such that theflow is suitable to impart, for example, a ‘vortical’ flow toaerosolized particles within and exiting the particle dispersion chamber10. In alternate embodiments, the ambient air channels 24 and ambientair channel orifices 26A are configured (e.g., within the wall 16A ofthe particle dispersion chamber 10) to operatively impart a different(e.g., randomized, turbulent, etc.) velocity vector (flow) pattern toaerosolized particles within and exiting the particle dispersion chamber10. According to preferred aspects, optimal particle size and velocityvector (particle flow) patterns afford efficient and effective targeteddelivery of aerosolized particles (e.g., atomized particles) to, forexample the nasal cavity and to regions thereof. In particularembodiments, the at least one ambient air channel 24 and orifice 26A arelocated in the wall 16A at or near the base (input opening) of theparticle dispersion chamber 10 and channel 22. Alternatively, the atleast one ambient air channel 24 and orifice 26A are located in the wall16A at any wall position along the longitudinal channel 22 axis suitableto impart a velocity vector flow pattern to particles within and exitingthe particle dispersion chamber 10 and channel 22 opening thereof.

The embodiments of the particle dispersion chamber 10 depicted in FIGS.2, 5 and 6, which include at least one ambient air channel 24 andcorresponding inner orifice 26A may optionally comprise an outer housing28 having a wall 30 defining a plenum space 31 between the outer housingwall 30 and wall 16A of the particle dispersion chamber 10. Preferably,the outer housing wall 30 comprises at least one opening 32, withoptional one-way valve 34. Preferably, the at least one ambient airchannel 24 and corresponding orifice 26A communicate with the at leastone opening 32 by means of the plenum space 31, such that, duringinhalation by user, inhaled air enters through opening 32 (see, e.g.,FIG. 6), and is directed through the plenum space 31 and further throughthe ambient air channel 24 and orifice 26A and into the internal channel22 of the particle dispersion chamber 10 to impart a flow pattern toparticles within and exiting the channel 22.

Intermediate Compressed Fluid Channel 40

In the embodiment depicted in FIGS. 7, 11, 14, and 19, the secondarycompressed fluid channel 8 communicates directly with the particledispersion chamber 10 via an intermediate compressed fluid channel 40.In addition to the secondary compressed fluid channel 8 for particlegeneration, the atomization means 11 may include a particle dispersionchamber feed channel 12 configured to communicate between the compressedfluid channel 8 and one or more directed fluid channels that include‘directed’ compressed fluid outlets 14 with corresponding compressedfluid outlet channel 18 and compressed fluid outlet orifices 20 withinthe wall 16A of the particle dispersion chamber 10 to provide forimparting a velocity vector pattern (e.g., ‘vortical,’ turbulent,randomized, etc.) to particles within and exiting the particledispersion chamber 10 and integrated atomizer 1.

In particular embodiments, the directed compressed fluid outlets 14comprise an outlet channel 18 through the wall 16A of the particledispersion chamber 10. The outlet channel 18 has a compressed fluidoutlet orifice 20 opening into the internal channel 22 of the particledispersion chamber 10. The outlet channel 18 and orifice 20 areconfigured to operatively direct compressed fluid tangentially and at anacute forward angle with respect the longitudinal axis of the internalchannel 22 of the particle dispersion chamber; that is, in suchembodiments the compressed fluid flow vector from the outlet orifice 20is directed tangentially with respect to the internal channel 22configuration, the flow vector having both radial and longitudinalcomponents with respect to the internal channel axis, such that the flowis suitable to impart, for example, a ‘vortical’ flow to aerosolizedparticles within and exiting the particle dispersion chamber 10. Inalternate embodiments, the outlet channels 18 and compressed fluidoutlet orifices 20 are configured (e.g., within the wall 16A of theparticle dispersion chamber 10) to operatively impart a different (e.g.,randomized, turbulent, etc.) flow to aerosolized particles within andexiting the particle dispersion chamber 10. According to preferredaspects of the present invention, optimal particle size and velocityvector patterns afford targeted delivery of aerosolized particles (e.g.,atomized particles) to, for example the nasal cavity and to regionsthereof.

In particular embodiments, the at least one compressed fluid outletchannel 18 and compressed fluid outlet orifice 20 is located in the wall16A at or near the upper end (output opening) of the particle dispersionchamber 10 and channel 22. Alternatively, the at least one outletchannel 18 and compressed fluid outlet orifice 20 is located in the wall16A at any wall position along the longitudinal channel 22 axis suitableto impart a velocity vector flow pattern to particles within and exitingthe particle dispersion chamber 10 and channel 22 opening thereof.

In particular preferred embodiments, and with reference to FIGS. 7 and11, there is a compressed fluid plenum space 36 defined by a dispersionchamber collar member 38. The compressed fluid plenum space 36communicates between the particle dispersion chamber feed channel 12 andthe at least one compressed fluid outlet channel 18 and compressed fluidoutlet orifice 20. In particular embodiments, the compressed fluidplenum space 36 communicates with the particle dispersion chamber feedchannel 12 through an intermediate compressed fluid channel 40, whichmay run externally, internally, or integrally with respect to the otherdevice elements.

In the embodiment depicted in FIGS. 14, and 19, the atomizer embodiment1 includes an extender portion 16E having a generally tube-like shapewith an input aperture 16F and an exit aperture 16G formed therein. Theextender portion 16E is coupled to the wall 16A of the particledispersion chamber 10 and extends the top of the particle dispersionchamber 10 thereby increasing the height of the particle dispersionchamber 10. The extender portion 16E receives particles into its inputaperture 16F from the exit aperture 16C of the particle dispersionchamber 10 and directs at least a portion thereof toward its exitaperture 16F. The extender portion may serve as the adapter for particledelivery to a user. Preferably, any of the adapters described below maybe fitted to the extender portion 16E and positioned to receiveparticles from its exit aperture 16G for delivery to the user and/orsurrounding environment. As shown in FIGS. 14, and 19, the dispersionchamber collar member 38 may be coupled to extender portion 16E therebydisposing the plenum space 36 between the dispersion chamber collarmember 38 and the extender portion 16E.

In the embodiments shown in FIGS. 14, and 19, the compressed fluidoutlets 14 are be formed in the extender portion 16E. The compressedfluid outlets 14 depicted include members 14A that extend between thechannel 22 and the plenum space 36 through the extender portion 16E. Themembers 14A may include one or more inwardly extending portions 14B thatextend into the particle dispersion chamber 10 or the extender portion16E. The one or more inwardly extending portions 14A may be configuredto direct the flow particles within the particle dispersion chamber 10.For example, the inwardly extending portions 14A may includeaerodynamically shaped baffles or fins configured to impart the velocityvector pattern into the particle flow. The members 14A may be generallytube shaped having compressed fluid outlet channel 18 and its compressedfluid outlet orifice 20 formed therein.

With reference to FIGS. 7, 14, and 19, preferably, embodimentscomprising one or more compressed fluid channels 18 and correspondingcompressed fluid outlet orifices 20, additionally comprise at least oneambient air channel 24 and corresponding inner orifice 26A (also shownin FIGS. 2, 5B, and 12, which depict embodiments without the compressedfluid channels 18). Such embodiments may optionally comprise an outerhousing 28 (see FIGS. 2, 6, and 7) having a wall 30 defining a plenumspace 31 between the outer housing wall 30 and wall 16A of the particledispersion chamber 10. The outer housing wall 30 has at least oneopening 32 in communication with ambient air, such that the ambient airchannel 24 and corresponding orifice 26B communicate with the at leastone opening 32 by means of the plenum space 31. Preferably, there is aone-way valve 34 (see FIGS. 2 and 6) in operative association with theat least one opening 32 of the outer housing wall 30.

Filtering Member 21

The aerodynamic particle size filtering member 21, as described herein,is fundamentally different from prior art impactors or impaction bafflesby virtue of its design and configuration and placement within or withrespect to the atomization chamber 4 and primary orifice 7. According topreferred aspects, the aerodynamic member 21 functions as a particlesize filter, by virtue of the fact that it is suitably positioned withrespect to the fluid flow and particle flow along the projected axis“F,” such that particles of desired size (e.g., 5 μm to 45 μm, 5 μm to50 μm, 7.5 μm to 40 μm, or 10 μm to about 30 μm microns) follow thecontour-directed fluid flow-stream and do not collide with the air-foilmember surface, while larger particles (e.g., greater than about 60 μm)collide with the air-foil member surface and are returned by means oflateral re-directing means of the air-foil member to the holding means(e.g., liquid reservoir portion 6).

The instant aerodynamic filtering member 21 (e.g., air-foil members)fundamentally differs from prior art impaction/stagnation baffles (jetorifice-proximate stagnation baffles) in that (i) a significantproportion of the atomized particles pass by the filtering member 21 inthe deflected fluid flow stream without impacting the filtering member21 providing for faster, more direct and efficient (less recycling,re-entrainment of liquid) particle delivery, and (ii) the filteringmember 21 is sufficiently distanced (by distance “J”) from theparticle-generating orifices 7 and 17, such that while the largerparticles collide with the air-foil and are redirected back to theholding means (e.g., liquid reservoir 6) for re-entrainment by theatomization means 11, they are not violently shattered into smallerparticles (as in the case of prior art impaction baffles) so that thefiltering member 21 serves as particle size filter and not asdroplet-shattering stagnation baffle to provide respirable particles,thus providing for a broader size range of deliverable particles,including, in view of the inventive improved secondary liquid feedchannel flow, particles from relatively viscous solutions noteffectively handled by prior art devices.

The filter member 21 has a contoured surface (e.g., an aerodynamicsurface contour) and is positioned at the distance “J” along theprojected axis “F” from the primary orifice plane “P” to provide anaerodynamic fluid flow around the contoured surface. In the embodimentdepicted in the figures, the distance “J” is greater than the distance“H.” In particular embodiments, the distance “J” along the projectedaxis “F” from the primary orifice plane “P” is greater than or equal to2×D1, 3×D1, 5×D1, 10×D1, 15×D1, 20×D1, 40×D1, or 50×D1.

According to preferred aspects, the configuration and positioning of thefilter member 21 along the projected axis “F” operationally provides,depending on particle size and/or mass, for a proportion of atomizedparticles that collide with the member and a proportion of non-collidingparticles (e.g., particles generated directly by the atomization means11, and directed therefrom towards the delivery or open end 4A of theatomization chamber 4 but which do not collide with the filter member 21by virtue of the relatively (compared to prior art) remote placement ofthe filter member 21 with respect to the primary compressed fluidorifice 7, and which non-colliding particles therefore do not depend oncollisional generation or lateral redirection by an impaction orstagnation baffle element). Such aspects may additionally provide fornon-colliding particles having paths near the surface of the particlefilter that are carried in the aerodynamic fluid flow around thecontoured surface of the filtering member 21.

Referring to FIG. 6, in some embodiments, the aerodynamic particle sizefilter member 21 is held at the distance “J” along the projected axis“F” by at least one filter support member 25 communicating with the wall2A of the atomization chamber 4, the support member 25 is configured tooperatively direct liquid accumulating on the filter member 21 away fromthe filter member for return to the liquid holding means. Preferably,there is a minimum number of such support members 25 to providesufficient support, and they are minimally configured (e.g., one or aminimum number of thin/slender radial or spoke-like support elements) sothat they minimally obstruct the particle flow path/volume, andminimally occlude the fluid and particle flow around the aerodynamicparticle size filter member 21. In particular aspects the supportmembers 25 are scalloped or otherwise contoured or slopped on theundersides 25A thereof, so as to direct liquid that accumulates on thefilter member 21 back to the holding means (e.g., liquid reservoir 6)for re-entrainment by the atomization means 11.

For example, FIGS. 5A and 5B show a particle filter member 21 supportedby three radial support arms 25. The support arms 25 support thefiltering member 21 at its upper portion (compressed fluidorifice-distal portion), and have curved or scalloped undersides 25A(compressed fluid orifice-proximal surfaces) that direct liquid,generated by particle collisions on the contoured surface of theparticle filter, laterally and downward to the holding means. Inoperation, the momentum of the colliding particles and the compressedfluid flow initially carries the resulting collisional liquid along thesurface of the filter member 21, in a direction away from theatomization means 11, and further to the support arms 25 whereupon theliquid flow is redirected laterally by the contoured surface (curvedundersides 25A) of the support arms 25, and in a direction generallytowards the atomization means 11 and eventually to the holding means.

It will be appreciated by one of ordinary skill in the relevant art thata variety of support designs and configurations could be used tosuitably support the filtering member 21, and provide collisional fluidredirecting means. For example, while three support arms 25 havingcurved or scallop undersides 25A are shown in the embodiment of FIGS. 5Aand 5B, any number of support arms 25 (including just one arm) might beused, and such arms could have a variety of surface contours (e.g.,angled, curved, grooved, ridged, convex, concave), and might be solid oralternatively comprised of sub-arm elements (e.g., multiple radialelements forming one, or each of a plurality of compound support arms).The essential aspect of such particle filter support means being thatthey suitably support the filtering member 21 at a distance of at least“H” from the compressed fluid orifice 7, and, at least preferably,provide collisional fluid redirecting means to return collisional fluidto the holding means for re-entrainment by the atomization means 11.

The support arms 25 of the filtering member 21 depicted in FIGS. 2, 5A,5B, 6, 7, and 11 radiate outwardly from the filtering member 21, whichis located near the center of the input opening 16B, in a substantiallyplanar fashion like the spokes of a wheel. In other words, the supportarms 25 may be substantially perpendicular to the wall 3 of theatomization chamber 4. In alternate embodiments, such as that depictedin FIGS. 12-14 and 18-19, the support arms 25 may extend upwardly ordownwardly to support the filtering member 21 at a distance of at least“H” from the compressed fluid orifice 7. In other words, the supportarms 25 may be at an angle other than substantially perpendicular withrespect to the wall 3 of the atomization chamber 4. Further, the angleof the support arms 25 relative to the wall 3 of the atomization chambermay be adjustable.

Preferably, as shown in the embodiment of FIG. 11, the surface contourof the filtering member 21 is aerodynamic and provides for anaerodynamic flow of fluid around the contour. However, a variety ofshapes and sizes of aerodynamic particle filters are encompassed.Preferably, the particle filter surface contour, and the configurationand positioning of the filtering member 21 along the projected axis “F”operationally provides (e.g., depending on particle size and/or mass)for a proportion of atomized particles that collide with the filteringmember 21 and a proportion of non-colliding particles. Suchnon-colliding particles are particles that are generated directly by theatomization means 11 and directed therefrom towards the delivery end ofthe atomization chamber 4, but which do not collide with the filtermember 21 by virtue the particle direction (velocity vector) and therelatively (compared to prior art) remote placement of the filteringmember 21 with respect to the compressed fluid orifice 7. Suchnon-colliding particles therefore do not depend on collisionalgeneration or lateral redirection by an impaction or stagnation baffleelement. Preferred aerodynamic surface contour aspects additionallyprovide for non-colliding particles having paths near the surface of thefiltering member 21 that escape collision with the filtering member 21by virtue of being carried in the aerodynamic fluid flow around thesurface of the filtering member 21.

Nasal Adapter 42

Certain embodiments, such as the atomizer embodiment 1 of, FIGS. 2 and7, additionally comprise a nasal adapter 42 in fluid communication withthe internal channel 22 (e.g., with the output opening 16C of theparticle dispersion chamber 10) of the particle dispersion chamber 10and thereby also in fluid communication with the atomization means 11 ofatomization chamber 4. The nasal adapter 42 is configured to operativelyreceive, via the internal channel 22 and output opening 16C of theparticle dispersion chamber 10, particles from the atomization means 11,and to sustain, and not disrupt, the particle flow or dispersion patterngenerated within and exiting from the internal channel 22 of theparticle dispersion chamber 10. In other words, the particles that exitthe atomization means 11 first travel through the internal channel 22where they are imparted with a predetermined flow pattern by theparticle dispersion chamber 10, then the particles travel into the nasaladapter 42 where they are routed or channeled into the nostrils of theuser without significant disruption of the predetermined flow pattern.As mentioned above, the extender portion 16E may be disposed between thenasal adapter 42 and the particle dispersion chamber 10. In suchembodiments, the extender portion 16E may impart a predeterminedparticle flow pattern to the atomized particles or alternatively maysimply allow at least a portion of the particles to flow from theparticle dispersion chamber 10 to the nasal adapter 42 withoutsignificant disruption of the predetermined flow pattern imparted by theparticle dispersion chamber 10.

For example, as shown in FIG. 7, the nasal adapter 42 communicatesbetween the particle dispersion chamber 10 and the lower portion (base)of a user's nose (not shown). Turning to FIGS. 8 and 9, the nasaladapter 42 includes a first interface portion 42B and a second interfaceportion 42C. The nasal adapter 42 may include a channel portion 42Ahaving an input aperture 42D formed in the first interface portion 42Band one or more exit apertures 42E formed in the second interfaceportion 42C.

In the embodiment shown in FIG. 7, the first interface portion 42B isconfigured to be coupled to the chamber wall 16 of the particledispersion chamber 10 near its output opening 16C and to receiveparticles therefrom. In alternate embodiments, the first interfaceportion 42B is configured to be coupled to the extender portion 16E nearits output opening 16G and to receive particles therefrom. In alternateembodiments, the nasal adapter 42 may include an integrally formedparticle dispersion chamber (not shown) that performs substantially thesame function(s) as the particle dispersion chamber 10. In suchembodiments, the first interface portion 42B is configured to be coupledto the atomization chamber 4 and receives particles therefrom via theopen portion 4A. In other words, the present invention includesembodiments in which the nasal adapter 42 and the particle dispersionchamber 10 are formed as a single unit and are coupled as a unit to theatomization chamber 4. Such a coupling may be effected using any methodknown in the art including using a connector such as a collar (notshown) substantially similar to the collar “C1,” a collar “C2” (see FIG.12 discussed below), and the like. Further, the filtering member 21 maybe disposed between the nasal adapter 42 and open portion 4A of theatomization chamber 4.

The second interface portion 42C is configured to interface with thenostrils of the user and to deliver particles thereto via the exitaperture(s) 42E. Preferably, the second interface portion 42C of thenasal adapter 42 is anthropometrically designed to conform to a humannose and seal around the nasal tissue to prevent the escaping ofparticles/droplets, while simultaneously sustaining the imparted flow(e.g., ‘vortical,’ randomized or turbulent, etc., flow) for entry intothe nasal aperture and subsequent penetration into the nasal cavity andtargeted regions thereof. Preferably, the second interface portion 42Cof the nasal adapter 42 is configured to conforms to the base of thenose. Preferably, the nasal adapter 42 provides a compact, portable,non-restrictive, non-invasive, easy to use device that provides asubstantially conforming seal over a broad range of individual nosesurface configurations to improve the efficiency of fluid, gas, ormedicament delivery thereto, and to preclude leakage or improperdelivery. The nasal adapter 42 provides for user comfort and suitabledecorum in public use.

Turning to FIGS. 8 and 9, preferably, the nasal adapter 42 facilitatesdelivery of airborne particles to a user's nasal channels by providingfor a temporary seal with the basal (underside) surface of the nose. Itshould be noted that FIGS. 8 and 9 depict two different exemplaryembodiments of the nasal adapter 42. However, for illustrative purposes,like reference numerals have been used in these figures to identifyidentical or substantially identical structures. For example, the secondinterface portion 42C of the nasal adapter 42 is sized and structured toconform to the basal surfaces of the nose, sealing around the nostrils(nares) allowing deliverable gas, fluid, or medicament to travel to thenasal chambers and beyond with minimal leakage. In preferredembodiments, a contoured lip 43, located on or integral with the exitaperture(s) 42E of the channel portion 42A comes into contact with thetissue tracing the contours of the basal surface of the nose. The secondinterface portion 42C and lip 43 comprise a generally horizontal planarand deformable surface that is placed in sealed communication with thebasal surface of the nose by application of upward pressure to hold thesecond interface portion 42C of the nasal adapter 42 against the basalsurface of the nose. Preferably, the shape of the nasal adapter 42 isadaptable to a variety of different nose sizes and contours, and/or canbe altered to fit noses of different sizes and contours. Sealing of theexit aperture(s) 42E of the second interface portion 42C of the nasaladapter 42 and the surrounding lip 43 to the basal surface of a user'snose is of significant utility. This aspect eliminates the difficultiesassociated with devices that completely cover or nearly completely coverthe nose, or that are in contact with the internal mucous membranes ofthe nose.

Additionally, in preferred dual delivery channel embodiments, the lip 43additionally sealably impinges on the columella nose base portion thatruns between the nostrils, to provide for separate nostril deliverychannels. Preferably, the nasal adapter 42 avoids the bulkiness and thepossibility of infections associated with devices that are inserted intothe nostrils, and allows for easy and comfortable communication with asmall surface area of the nose to provide for relatively inconspicuousapplications outside clinical settings. Preferred nasal adaptors aredescribed in WO2004US0028874 (Pub. No. WO05023334A3; incorporated byreference herein in its entirety). In particular aspects, the nasaladapter 42, as shown in FIG. 8, may have a single divider 44 to helpchannel the particles (e.g., imparted droplet flow) into the appropriatenasal aperture. Alternatively, as shown in FIG. 9, the exit aperture(s)42E of the nasal adapter 42 may include one or more, and preferably two,oriented openings 46, configured to channel the droplets/particles intoa particular region of the naris plane (plane defined by the nasalopening), for example, the front part of the nasal apertures.Alternatively, oriented openings 46 are disposed at or near the rear ofthe second interface portion 42C to direct droplet/particle flow intothe back part of the corresponding nasal apertures (closest to thelips).

According to particular aspects, such oriented openings 46 havesubstantial utility to more selectively target particle delivery withinthe nasal cavity, and regions thereof, of a user. For example, it hasbeen shown that air that flows through a specific region of the nasalcavity originates at a specific location on the external naris plane(Zhao et al., Chem. Senses, 29:365-379, 2004; incorporated herein byreference in its entirety). For example, only air that enters the distal(ventral) tip of the nares reaches the olfactory region (Id; FIG. 7 atpage 369). Therefore, nasal delivery using the inventive devices can becustomizes with respect to left or right nostrils, and with respect totarget regions within the respective nasal cavities, to provide for moreprecise and effective drug/agent targeting and delivery. Suchembodiments comprising nasal adapters with, or in communication withoriented openings provide for additional olfactory utilities. Forexample, devices having oriented openings 46, configured to channel thedroplets/particles into the front part of the naris plane have,according to additional inventive aspects, substantial utility forenhancing olfaction and effective olfactory sensitivity. For example,such embodiments have utility for facilitating olfaction of scented(e.g., perfume, fragrance, essential oil or cosmeceutical agent) and/orfood and/or beverage (e.g., wine) products.

Nasal Adapter 60

FIGS. 13-17 depict a nasal adapter 60 configured for insertion into oneor both nostrils of the user. The nasal adapter 60 includes a firstinterface portion 60B and at least one second interface portion 60C. Thenasal adapter 60 may include a channel portion 60A having an inputaperture 60D formed in the first interface portion 60B and one or moreexit apertures 60E formed in each of the second interface portions 60C.

As is apparent to those of ordinary skill, the open portion 4A of theatomization chamber 4 may be larger than the nostril of the user.Consequently, as illustrated in FIGS. 13-15A and 16-17, the nasaladapter 60 configured for insertion into a single nostril may begenerally cone or funnel shaped, tapering from the larger open portion4A of the atomization chamber 4 to the smaller nostril of the user.However, as is appreciated by those of ordinary skill, the embodimentsin which the open portion 4A of the atomization chamber 4 issubstantially the same size or smaller than the nostril of the user arealso within the scope of the present invention. Further, in embodimentsin which the open portion 4A of the atomization chamber 4 is larger thanthe nostril of the user, the reduction in size from the first interfaceportion 60B to the second interface portion 60C need not be along a coneor equivalently tapered shape. Instead, any shape known in the art maybe used, including a stepped-down shape, pyramidal shape, arbitraryshape, and the like.

In the embodiment depicted in FIGS. 13-15A and 16-17, the cone-shape ofthe nasal adapter 60 extends in a generally linear direction (e.g., thedirection of the axis “F”). To use the nasal adapter 60, the user mayhold his/her head in an upright position and insert the second interfaceportion 60C into his/her nostril.

In the embodiment shown in FIG. 14, the first interface portion 60B isconfigured to be coupled to the extender portion 16E near its outputopening 16G and to receive particles therefrom. The nasal adapter 60 isin fluid communication with the internal channel 22 (e.g., with theoutput opening 16C of the particle dispersion chamber 10) of theparticle dispersion chamber 10 via the extender portion 16E and isthereby also in fluid communication with the atomization means 11 ofatomization chamber 4. The nasal adapter 60 is configured to operativelyreceive particles from the atomization means 11, and to sustain, and notdisrupt, the particle flow or dispersion pattern of the particlesreceived. In other words, the particles that exit the atomization means11 first travel through the internal channel 22 where they are impartedwith a predetermined flow pattern by the particle dispersion chamber 10,then the particles travel through the extender portion 16E and into theoral adapter 80 where they are routed or channeled into the nostril ofthe user without significant disruption of the predetermined flowpattern. After entering the nostril, the particles may be directedtoward the user's nasal cavities for absorption into the body thereby,in a manner described above with respect to nasal adapter 42. Theoverall shape of the nasal adapter 60 and/or its exit aperture(s) 42Emay be modified to selectively target particle delivery within the nasalcavity, and regions thereof, of a user, in a manner described above withrespect to nasal adapter 42.

In alternate embodiments, such as the embodiment depicted in FIG. 13,the particle dispersion chamber 10 may be omitted. Alternatively, thenasal adapter 60 may include an integrally formed particle dispersionchamber (not shown) that performs substantially the same function(s) asthe particle dispersion chamber 10. In such embodiments, the firstinterface portion 60B is configured to be coupled to the atomizationchamber 4 and receives particles therefrom via the open portion 4A. Inother words, the present invention includes embodiments in which theparticle dispersion chamber 10 is omitted as well as embodiments inwhich the oral adapter 80 includes an integrally formed particledispersion chamber 10. In such embodiments, the filtering member 21 maybe disposed between the nasal adapter 60 and the open portion 4A of theatomization chamber 4.

In the embodiment depicted in FIG. 13, the connector or collar “C2” isdisposed between the first interface portion 60B and the atomizationchamber 4. The collar “C2” may include a recessed portion “R3”configured to receive the first interface portion 60B of the oraladapter 80 and position the input aperture 60D of the channel portion60A adjacent to the open portion 4A formed in the top of the atomizationchamber 4. The collar “C2” includes a recessed portion “R4” configuredto receive a portion of the filtering member 21 and rest thereupon. Thecollar “C2” may also have a portion C2-A that rests upon an upperportion the wall 3 of the atomization chamber 4.

The second interface portion 60C is configured to interface with thenostril of the user and to deliver particles therein via the exitaperture(s) 60E. Preferably, the second interface portion 60C of thenasal adapter 60 is anthropometrically designed to fit inside a humannostril and to prevent adequately the escape of particles/droplets,while simultaneously sustaining the imparted flow (e.g., ‘vortical,’randomized or turbulent, etc., flow) for entry into the nostril andsubsequent penetration into the inside of the nasal cavity and targetedregions thereof.

As illustrated in FIG. 13, the nostril adapter 60 may include anoptional sleeve 70 fitted over one or more of its second interfaceportions 60C. The sleeve 70 may include an aperture 72 located adjacentto the exit aperture(s) 60E for permitting the passage ofparticles/droplets therethrough. The sleeve 70 may be removable andreusable or disposable allowing the nasal adapter 60 to be usedrepeatedly between cleanings and/or replacement by simply replacing thesleeve 70 after one or more uses of the nasal adapter 60.

FIGS. 15A and 16-17 provide several non-limiting examples ofconfigurations of the nostril adapter 60 having a single secondinterface portion 60C. Each of these embodiments is configured to directthe particle flow to a particular selected area within the nasal cavity.FIG. 15 depicts a generally conically shaped nasal adapter 60 like thatdepicted in FIG. 13 (without the sleeve 70). The conically shaped nasaladapter 60 tapers along a generally linear direction (e.g., thedirection of the axis “F”) and includes a substantially centered singleexit aperture 60E. FIG. 16 depicts a nasal adapter 60 having asubstantially conically shaped portion 61 similar to that of the nasaladapter 60 depicted in FIG. 15. However, the second interface portion60C of the nasal adapter 60 of FIG. 16 has an angled or bent portion 62and a sloped upper portion 63 with a single exit aperture 16E formedtherein. These structures may direct the particle flow toward a selectedtarget area within the nostril and/or may make the nostril adapter 60more comfortable to the user. The nasal adapter of FIG. 17 is somewhatcone-shaped and includes an off center exit aperture 60E as well as thesloped upper portion 63 with a single exit aperture 16E formed therein.

FIG. 15B depicts a nasal adapter 60 having a pair of second interfaceportions 60C, each configured to be inserted into one of the nostrils ofthe user. In other words, the nasal adapter 60 depicted in FIG. 15B isconfigured for dual delivery. The dual delivery nasal adapter 60includes a portion 64 configured to receive a portion of the columellanose base portion that runs between the nostrils. The dual deliverynasal adapter 60 embodiment depicted includes a pair of substantiallycone-shaped members 65A and 65B merged together below a location spacedfrom the exit aperture(s) 60E of each of the second interface portions60C. The merged substantially cone-shaped members 65A and 65B define acontinuous interior cavity (not shown) configured to receive particlesfrom the extender portion 16E and/or the particle dispersion chamber 10.The portion 64 may be located between the substantially cone-shapedmembers 65A and 65B at the location where the substantially cone-shapedmembers 65A and 65B merge. The portion 64 may have general saddle-likeshape.

With respect to each of the nasal adapters depicted in FIGS. 13-17, theexit aperture(s) 16E and/or second interface portion(s) 60C may beconfigured to selectively target particle delivery within the nasalcavity, and regions thereof, of a user in a manner identical to orsimilar to that discussed above with respect to the nasal adapter 42.The nasal adapter 60 may provide a compact, portable, non-restrictive,non-invasive, easy to use device that may be readily configured for abroad range of individual nostril configurations to improve theefficiency of fluid, gas, or medicament delivery thereto, and topreclude leakage or improper delivery. The nasal adapter 60 provides foruser comfort and suitable decorum in public use.

Ocular Adapter 48

As show in FIGS. 10 and 11, particular embodiments comprise an ocularadapter 48. The ocular adapter 48 is configured to operatively receiveparticles from the atomization means 11, and to sustain, and notdisrupt, the particle flow or dispersion pattern generated within andexiting from the internal channel 22 of the particle dispersion chamber10. In the embodiment depicted in the drawings, the particles that exitthe atomization means 11 first travel through the internal channel 22where they are imparted with a predetermined flow pattern by theparticle dispersion chamber 10, then the particles travel into theocular adapter 48 where they are routed or channeled onto the surface ofthe eye of the user without significant disruption of the predeterminedflow pattern. The filtering member 21 may be disposed between the ocularadapter 48 and output opening 16C of the particle dispersion chamber 10.Optionally, the extender portion 16E may be disposed between theparticle dispersion chamber 10 and the ocular adapter 48.

Like the nasal adapter 42, the ocular adapter 48 includes a firstinterface portion 48B and a second interface portion 48C. The ocularadapter 48 may include a channel portion 48A having an input aperture48D formed in the first interface portion 48B and one or more outletopenings 48E formed in the second interface portion 48C.

The first interface portion 48B is configured to be coupled to thechamber wall 16 of the particle dispersion chamber 10 near its outputopening 16C and to receive particles therefrom. In alternateembodiments, the ocular adapter 48 may include an integrally formedparticle dispersion chamber (not shown) that performs substantially thesame function(s) as the particle dispersion chamber 10. In suchembodiments, the first interface portion 48B is configured to be coupledto the atomization chamber 4 and receives particles therefrom via theopen portion 4A. In other words, the present invention includesembodiments in which the ocular adapter 48 and the particle dispersionchamber 10 are formed as a single unit and are coupled as a unit to theatomization chamber 4. Such a coupling may be effected using any methodknown in the art including using a connector such as a collar (notshown) substantially similar to the collar “C1,” the collar “C2” (seeFIG. 12 discussed below), and the like. In such embodiments, thefiltering member 21 may be disposed between the ocular adapter 48 andopen portion 4A of the atomization chamber 4.

The second interface portion 48C is configured to interface with thesurface of the eye of the user and to deliver particles thereto via theoutlet opening(s) 48E. Preferably, the second interface portion 48C ofthe ocular adapter 48 is anthropometrically designed to conform to ahuman eye socket and seal around the tissue or surfaces surrounding theeye to prevent the escaping of particles/droplets, while simultaneouslysustaining the imparted flow (e.g., ‘vortical,’ randomized or turbulent,etc., flow) for delivery to the eye and/or targeted regions thereof.

Preferably, the second interface portion 48C of the ocular adapter 48conforms to the facial portions surrounding the eye socket. Preferably,the ocular adapter 48 provides a compact, portable, non-restrictive,non-invasive, easy to use device that provides a good conforming sealover a broad range of individual eye socket surface configurations toimprove the efficiency of fluid, gas, or medicament delivery thereto,and to preclude leakage or improper delivery. The ocular adapter 48provides for user comfort and suitable decorum in public use.Preferably, the ocular adapter 48 facilitates delivery of airborneparticles to a user's eye by providing for a temporary seal with thefacial surfaces surrounding the eye.

For example, the second interface portion 48C of the ocular adapter 48is sized and structured to conform to the surfaces around the eyeallowing deliverable gas, fluid, or medicament to travel to the eye withminimal leakage. In preferred embodiments, a lip 49, located on orintegral with the outlet opening(s) 48E of the channel portion 42A comesinto contact with the tissue tracing the contours of the eye socketarea. The second interface portion 48C and lip 49 comprise a generallyhorizontally planar and deformable surface that is placed in sealedcommunication with the surfaces surrounding the eye by application ofupward pressure (i.e., pressure in the direction of the eye) to hold theocular adapter 48 against the surrounding surfaces.

Preferably, the shape of the ocular adapter 48 is adaptable to a varietyof different eye sizes and contours, and/or can be altered to fit eyesof different sizes and contours. Sealing of the outlet opening(s) 48Eand the surrounding lip 49 to the surfaces surrounding a user's eye isof significant utility. Preferably, the ocular adapter 48 avoids thebulkiness and the possibility of infections and injury associated withdevices that are inserted close to the eye, and allows for easy andcomfortable communication with a small surface area of the face toprovide for relatively inconspicuous applications outside clinicalsettings.

Oral Adapter 48

Certain embodiments, such as the atomizer embodiment 1 of FIGS. 18-19,additionally comprise an oral adapter 80. The oral adapter 80 includes afirst interface portion 80B and a second interface portion 80C. The oraladapter 80 may include a channel portion 80A having an input aperture80D formed in the first interface portion 80B and one or more exitapertures 80E formed in the second interface portion 80C.

As is apparent to those of ordinary skill, the open portion 4A of theatomization chamber 4 may be larger than the mouth of the user.Consequently, as illustrated in FIGS. 18-21, the oral adapter 80 may begenerally cone or funnel shaped. The oral adapter 80 may be bent orcurved so that the user may hold his/her head in an upright positionwhile using the oral adapter 80. Alternatively, the oral adapter 80 mayextend along a generally linear direction (e.g., the direction of theaxis “F”). To use such an embodiment of the oral adapter 80, the usermay tip his/her head downward to place the second interface portion 80Cinto his/her mouth.

In the embodiment shown in FIG. 19, the first interface portion 80B isconfigured to be coupled to be coupled to the extender portion 16E nearits output opening 16G and to receive particles therefrom. The oraladapter 80 is in fluid communication with the internal channel 22 (e.g.,with the output opening 16C of the particle dispersion chamber 10) ofthe particle dispersion chamber 10 via the extender portion 16E and isthereby also in fluid communication with the atomization means 11 ofatomization chamber 4. The oral adapter 80 is configured to operativelyreceive particles from the atomization means 11, and to sustain, and notdisrupt, the particle flow or dispersion pattern of the particlesreceived. In other words, the particles that exit the atomization means11 first travel through the internal channel 22 where they are impartedwith a predetermined flow pattern by the particle dispersion chamber 10,then the particles travel through the extender portion 16E and into theoral adapter 80 where they are routed or channeled into the mouth of theuser without significant disruption of the predetermined flow pattern.After entering the mouth, the particles may be directed toward theinside of the user's cheeks for absorption into the body thereby. Theoverall shape of the oral adapter 80 and/or its exit aperture(s) 80E maybe modified to selectively target particle delivery within the mouth,and regions thereof, of a user, in a manner similar to that describedabove with respect to nasal adapter 42.

In alternate embodiments, such as the one depicted in FIG. 18, theparticle dispersion chamber 10 may be omitted. In further alternateembodiments, the oral adapter 80 may include an integrally formedparticle dispersion chamber (not shown) that performs substantially thesame function(s) as the particle dispersion chamber 10. The firstinterface portion 80B may be configured to be coupled to the atomizationchamber 4 and receives particles therefrom via the open portion 4A. Inother words, the present invention includes embodiments in which theparticle dispersion chamber 10 is omitted as well as embodiments inwhich the oral adapter 80 includes an integrally formed particledispersion chamber 10. In such embodiments, the filtering member 21 maybe disposed between the oral adapter 80 and the open portion 4A of theatomization chamber 4.

In the embodiment depicted in FIG. 18, a connector or collar “C2” isdisposed between the first interface portion 80B and the atomizationchamber 4. The collar “C2” may include a recessed portion “R3”configured to receive the first interface portion 80B of the oraladapter 80 and position the input aperture 80D of the channel portion80A adjacent to the open portion 4A formed in the top of the atomizationchamber 4. The collar “C2” includes a recessed portion “R4” configuredto receive a portion of the filtering member 21 and rest thereupon. Thecollar “C2” may also have a portion C2-A that rests upon an upperportion the wall 3 of the atomization chamber 4.

The second interface portion 80C is configured to interface with themouth of the user and to deliver particles thereto via the exitaperture(s) 80E. Preferably, the second interface portion 80C of theoral adapter 80 is anthropometrically designed to fit inside a humanmouth and allow the user's lips to seal thereabout to prevent theescaping of particles/droplets, while simultaneously sustaining theimparted flow (e.g., ‘vortical,’ randomized or turbulent, etc., flow)for entry into the mouth and subsequent penetration into the inside ofthe mouth (e.g., cheeks) and targeted regions thereof.

As illustrated in FIGS. 20 and 21, the oral adapter 80 may include anoptional mouthpiece 90 fitted over or coupled to its second interfaceportion 80C. The mouthpiece 90 may include an aperture 92 locatedadjacent to the exit aperture(s) 80E for permitting the passage ofparticles/droplets therethrough. The mouthpiece 90 may be removable andreusable or disposable allowing the oral adapter 80 to be usedrepeatedly between cleanings and/or replacement by simply replacing themouthpiece 90 after one or more uses of the oral adapter 80.

In the embodiment depicted in FIG. 20, the mouthpiece 90 and itsaperture 92 are bifurcated by one or more baffles 94. The baffle(s) 94may be configured to direct the particle flow. In some embodiments, thebaffles 94 may direct the particle flow toward the inside surface of thecheeks of the user. The baffles 94 may provide structural support thathelps maintain the shape of the second interface portion 80C, the exitaperture(s) 80E, the mouthpiece 90 and/or the aperture 92 of themouthpiece 90.

In the embodiment depicted in FIG. 21, the mouthpiece 90 includes aclosed end portion 96 located opposite the exit aperture(s) 80E of thesecond interface portion 80C of the oral adapter 80. The mouthpiece 90also includes a first and second exit aperture 98A and 98B located onopposite sides of the mouthpiece 90. The first and second exit apertures98A and 98B are positioned to be juxtaposed with the inside surfaces ofthe cheeks of the user when the mouthpiece 90 is received inside themouth of the user. In this manner, particles exiting the mouthpiece 90via the first and second exit apertures 98A and 98B are directed towardthe inside surface of the user's cheeks. Particles that encounter theinside of the cheeks of the user may be absorbed thereby.

In embodiments that include the oral adapter 80, the atomizer embodiment1 may be “driven” by a compressed fluid originating from the compressedfluid source (not shown) and flowing through the primary compressedfluid channel 13. Alternatively, the user may “drive” the device byinhaling through the oral adapter 80 thereby drawing fluid inwardlythrough the primary compressed fluid channel 13. This fluid mayencounter the liquid in the primary liquid feed channel 15 in a mannersimilar to that described above with respect to compressed gas suppliedby the compressed gas source.

The oral adapter 80 may provide a compact, portable, non-restrictive,non-invasive, easy to use device that provides a substantiallyconforming seal over a broad range of individual mouth configurations toimprove the efficiency of fluid, gas, or medicament delivery thereto,and to preclude leakage or improper delivery. The oral adapter 80 mayalso provide for user comfort and suitable decorum in public use.

Alternate Embodiment

FIGS. 22-24 depict an alternate embodiment of the inventive atomizer, anatomizer 100, configured to deliver aerosolized particles into theatmosphere. The atomizer 100 includes an atomization housing 102configured to house a portion of the component of the atomizer 100, suchas the atomization means 11′. The atomization means 11′ functions insubstantially the same manner as atomization means 11 (described above).The atomization means 11′ is substantially similar to the atomizationmeans 11 described above and differs therefrom only with respect to theshape and positioning of its components. Like components have beenidentified with identical reference numerals. Only components thatdiffer from those of the atomization means 11 are described in detail.

Unlike, the atomizer 1 described above, which includes the housing 2having an atomization chamber 4 formed therein, the housing 102 includesa recessed portion 102D configured to receive the liquid holding means,such as an ampoule, a container 106, and the like, that may be at leastpartially filled with the liquid (not shown), such as a perfume,fragrance, essential oil or cosmeceutical agent, medicament, airfreshener, insect repellent, insecticide, sanitizer, paint, and thelike. The recessed portion 102D may circumscribe a portion of theatomization means 11′. A bottom surface 102E of the recessed portion102D may be tapered toward an aperture 102F formed therein. Thecontainer 106, which is configured to be received inside the recessedportion 102D may have a hollow ring-like shaped housing 106F with atapered bottom portion 106A that tapers toward an aperture 106B formedin tapered bottom portion 106A. The aperture 106B is juxtaposed with theaperture 102F formed in the recessed portion 102D when the container 106is received therein. The tapered bottom portion 106A may cause theliquid stored inside the container 106 to flow toward the aperture 106B,through the aperture 106B, and into the aperture 102F. The container 106has a tapered top portion 106D that tapers toward an aperture 106Eformed in tapered top portion 106D. The tapered top portion 106D may beapproximately parallel with the tapered bottom portion 106A.

In the embodiment depicted in the drawings, the container 106 has anopen-ended channel 106C configured to receive a portion of theatomization means 11′ when the container 106 is received inside therecessed portion 102D. A portion 11′-A of the atomization means 11′extends upwardly above the container 106.

The atomization means 11′ includes a primary liquid feed channel 15 incommunication with the liquid held in the container 106. The primaryliquid feed channel 15 may receive the liquid from a secondary liquidfeed channel 5′ that is in fluid communication with the container 106.In other words, the secondary liquid feed channel 5′ is intermediatebetween the primary liquid feed channel 15 and the container 106. Thesecondary liquid feed channel 5′ differs from the secondary liquid feedchannel 5 of the atomizer 1, which is generally linear in shape, in thatthe secondary liquid feed channel 5′ includes one or more bent portions5′-A, 5′-B, and 5′-C. The bent portions 5′-A, 5′-B, and 5′-C areconfigured to position an inlet 5′-D of the secondary liquid feedchannel 5′ in fluid communication with the aperture 106B of thecontainer 106. Liquid exiting the container 106 is received into thesecondary liquid feed channel 5′ through the inlet 5′-D and istransported by the secondary liquid feed channel 5′ up to the primaryliquid feed channel 15 in the same manner liquid is transported by thesecondary liquid feed channel 5 of the atomizer 1 (described above).

The atomization means 11′ may be driven by a compressed fluid source(not shown). In such embodiments, the atomization means 11′ includes aprimary compressed fluid channel 13 in communication with an external orinternal compressed fluid source (not shown). As described above, theprimary compressed fluid channel 13 has the corresponding orifice 7defining a projectable longitudinal compressed fluid feed channel axis“F,” in operative communication with the primary liquid feed channel 15and its corresponding orifice 17. The primary compressed fluid channel13 receives compressed fluid from a secondary compressed fluid channel 8in fluid communication with the compressed fluid source (not shown). Inother words, the secondary compressed fluid channel 8 is intermediatebetween the primary compressed fluid channel 13 and a source ofcompressed fluid. The atomization means 11′ is suitably configured toentrain a liquid in a fluid flow stream (not shown) to generate aparticle (e.g., aerosolized liquid droplet) flow along (e.g., centeredalong) the projected axis “F.”

Optionally, the atomizer 100 may include a combination atomizationchamber and particle dispersion chamber 110 mounted to the housing 102.The chamber 110 is in fluid communication with the atomization means11′. The portion 11′-A of the atomization means 11′ may extend up intothe chamber 110.

The chamber 110 may help define the particle size after the droplets arecreated by and received from the atomization means 11′. The chamber 110includes a housing 116 having an internal laterally extending wall 116A.The wall 116A abuts the tapered top portion 106D of the container 106when the chamber 110 is mounted to the housing 102. The wall 116Aincludes an opening 116B, configured to receive the portion 11′-A of theatomization means 11′ and allow the portion 11′-A to extend into thechamber 110 thereby allowing the liquid stored in the container 106 tobe atomized inside the chamber 110. The wall 116A includes a liquidreturn aperture 116C juxtaposed with the aperture 106E formed in taperedtop portion 106D of the container 106. To reduce evaporation of theliquid housed inside the container 106, a one-way valve (not shown) orseal (not shown) may be disposed inside the liquid return aperture 116Cand/or the aperture 106E. The wall 116A may taper toward the liquidreturn aperture 116C to encourage liquid on the wall 116A inside thechamber 110 to flow into the liquid return aperture 116C, through theaperture 106E, and into the container 106. Particles contacting theinside surface of the of the housing 116 may travel downward to theinternal laterally extending wall 116A, flow down the wall 116A into theliquid return aperture 116C, flow through the aperture 116C into theaperture 106E, and finally return to the container 106 forre-atomization by the atomization means 11′.

The chamber 110 includes an atomization chamber-distal output opening116D, and an internal particle dispersion channel 122 communicatingbetween the portion 11′-A of the atomization means 11′ and the outputopening 116D. In some embodiments, the chamber 110 helps impart avelocity vector or flow pattern (e.g., ‘vortical,’ randomized,turbulent, etc. flow) to the aerosolized particles (e.g., atomizedparticles) received within and exiting from the chamber 110. Methods andstructures for imparting a desired velocity vector or flow pattern aredescribed above with respect to the particle dispersion chamber 10 andany methods or structures discussed above may be used with orincorporated into chamber 110.

The chamber 110 may include a connector portion 116E configured tooperably couple the chamber 10 to the housing 102. In the embodimentdepicted in the drawings, the housing 102 includes a threaded portion102G formed along a portion of its outside surface. The connectorportion 116E includes a threaded portion 116F configured for threadedengagement with the threaded portion 102G of the housing 102. Thethreaded portions 102G and 116F may be configured to position the liquidreturn aperture 116C adjacent to the aperture 106E formed in tapered topportion 106D when fully engaged with one another (i.e., the threadedconnection between threaded portions 102G and 116F is tight).Alternatively, the chamber 10 may be coupled to the housing 102 by acollar (not shown) like the collar “C1” or its equivalent.

The atomizer 100 may optionally include the aerodynamic particle-sizefiltering means or filtering member 21 (e.g., air-foil member) suitablyconfigured and positioned at a distance “J” from the primary orificeplane “P” to direct fluid flow around its contour, and therebynon-collisionally redirect particle flow of the desired particle sizerange around its contour, while simultaneously blocking larger particlesfor return to the container 106 and re-entrainment. As is apparent tothose of ordinary skill in the art, the filtering member 21 may beinstalled inside the particle dispersion chamber 110 at distance “J”from the primary orifice plane “P.” Particles filtered from the particleflow may travel down the inside surface of the housing 116, along theinternal laterally extending wall 116A, into the liquid return aperture116C, into the aperture 106E, and finally into the container 106.

The internal channel 122 of the chamber 110 may be configured so as tosustain, and not disrupt, the particle flow or dispersion patterngenerated therein and exiting therefrom through the output opening 116D.Therefore, the internal channel 122 is, for example, cylindrical orsubstantially cylindrical (e.g., slightly tapered), smooth taperedcylindrical, etc., such that there are no abrupt discontinuities alongthe internal surface thereof, or surface structures or elementsextending within the internal channel 122, or end caps, restrictions orelements that restrict the output opening 116D of the channel 122, thatwould disrupt the flow pattern imparted to the particles within theinternal channel 122 and exiting the output opening 116D thereof.

As is apparent to those of ordinary skill, atomizers and nebulizers maybe configured for use with various accessories, adapters, and the likeand the atomizer 100 is not limited to use with any particularaccessories, adapters, and the like. For example, using the techniquesdescribed herein, the nasal adapter 42 (or any adapter described herein)may be coupled to the chamber 110 and configured to receive atomizedparticles from output opening 116D.

Alternate Embodiment

FIGS. 25-26 depict another alternate embodiment of the inventiveatomizer, an atomizer 200, configured to deliver aerosolized particlesinto the atmosphere. The atomizer 200 includes an atomization housing202 configured to house a portion of the component of the atomizer 200,such as the atomization means 11″. The atomization means 11″ functionsin substantially the same manner as atomization means 11 (describedabove). The atomization means 11′ is substantially similar to theatomization means 11 described above and differs therefrom only withrespect to the shape and positioning of its components. Like componentshave been identified with identical reference numerals. Only componentsthat differ from those of the atomization means 11 are described indetail.

Unlike, the atomizer 1 described above, which includes the housing 2having an atomization chamber 4 formed therein, the housing 202 includesa recessed portion 202D configured to receive the liquid holding means,such as an ampoule, a container 206, and the like, that may be at leastpartially filled with the liquid (not shown), such as a perfume,fragrance, essential oil or cosmeceutical agent, medicament, airfreshener, insect repellent, insecticide, sanitizer, and the like. Therecessed portion 202D may circumscribe a portion of the atomizationmeans 11″. A bottom surface 202E of the recessed portion 202D may betapered toward an aperture 202F formed therein. The container 206, whichis configured to be received inside the recessed portion 202D may have aring-like shaped housing 206F with a tapered bottom portion 206A thattapers toward an aperture 206B formed in tapered bottom portion 206A.The aperture 206B is juxtaposed with the aperture 202F formed in therecessed portion 202D when the container 206 is received therein. Thetapered bottom portion 206A may cause the liquid stored inside thecontainer 206 to flow toward the aperture 206B, through the aperture206B, and into the aperture 202F. The exemplary container 206 has anopen top portion 206D.

In the embodiment depicted in the drawings, the container 206 has anopen-ended channel 206C configured to receive a portion of theatomization means 11″ when the container 206 is received inside therecessed portion 202D. A portion 11″-A of the atomization means 11″extends upwardly above the container 206.

The atomization means 11″ includes a primary liquid feed channel 15 incommunication with the liquid held in the container 206. The primaryliquid feed channel 15 may receive the liquid from a secondary liquidfeed channel 5″ that is in fluid communication with the container 206and an external reservoir 300 such as an ampoule, a container, and thelike. In other words, the secondary liquid feed channel 5″ isintermediate between the primary liquid feed channel 15 and both thecontainer 206 and the external reservoir 300.

The secondary liquid feed channel 5″ differs from the secondary liquidfeed channel 5 of the atomizer 1, which has a single inlet, in that thesecondary liquid feed channel 5″ has an inlet 5″-D in communication withthe container 206 and an inlet 5″-E in communication the externalreservoir 300. The secondary liquid feed channel 5″ also includes achannel section 5″-H that branches from the majority portion of thesecondary liquid feed channel 5″ to position the inlet 5″-D incommunication with the container 206. Further, a portion 5″-F of thesecondary liquid feed channel 5″ exits the housing 202 and extendslaterally therefrom. The external reservoir 300 is mounted to a distalend portion 5″-G of the secondary liquid feed channel 5″. The externalreservoir 300 has an exit aperture 310 configured to supply the liquidto the inlet 5″-E.

The secondary liquid feed channel 5″ also differs from the secondaryliquid feed channel 5 of the atomizer 1, which is generally linear inshape, in that the secondary liquid feed channel 5′ includes one or morebent portions 5″-A, 5″-B, and 5″-C. The bent portions 5″-A, 5″-B, and5″-C are configured to position an inlet 5″-D of the secondary liquidfeed channel 5″ in fluid communication with the aperture 206B of thecontainer 206 and inlet 5″-E in fluid communication with the externalreservoir 300. Liquid received into the container 206 exits therefromthrough the aperture 206B and enters into the secondary liquid feedchannel 5″ through the inlet 5″-D. Liquid housed in the externalreservoir 300 exits therefrom through the exit aperture 310 and entersinto the secondary liquid feed channel 5″ through the inlet 5″-E. Liquidin the secondary liquid feed channel 5″ is then transported by thesecondary liquid feed channel 5″ up to the primary liquid feed channel15 in the same manner liquid is transported by the secondary liquid feedchannel 5 of the atomizer 1 (described above).

The atomization means 11″ may be driven by a compressed fluid source(not shown). In such embodiments, the atomization means 11″ includes aprimary compressed fluid channel 13′ in communication with an externalor internal compressed fluid source (not shown). As described above, theprimary compressed fluid channel 13 has the corresponding orifice 7defining a projectable longitudinal compressed fluid feed channel axis“F,” in operative communication with the primary liquid feed channel 15and its corresponding orifice 17. The primary compressed fluid channel13 receives compressed fluid from a secondary compressed fluid channel 8in fluid communication with the compressed fluid source (not shown). Inother words, the secondary compressed fluid channel 8 is intermediatebetween the primary compressed fluid channel 13 and a source ofcompressed fluid. The atomization means 11″ is suitably configured toentrain a liquid in a fluid flow stream (not shown) to generate aparticle (e.g., aerosolized liquid droplet) flow along (e.g., centeredalong) the projected axis “F.”

In the embodiments depicted in the figures, a tapered section is locatedbetween the primary and secondary channels of the atomization means 11,atomization means 11′, and atomization means 11″. In other words, afirst tapered section T1 is located between the primary compressed fluidchannel 13 and the secondary compressed fluid channel 8 and a secondtapered section T2 is located between the primary liquid feed channel 15and the secondary liquid feed channel 5. Similarly, the second taperedsection T2 is located between the primary liquid feed channel 15 and thesecondary liquid feed channel 5′ and the second tapered section T2 islocated between the primary liquid feed channel 15 and the secondaryliquid feed channel 5″. The lengths of each channel 13, 8, 15, and 5 mayvary depending upon the application. Further, the length of the firsttapered section T1 and the second tapered section T2 may also vary. Inthe embodiments depicted in the figures, the second tapered section T2of the atomizer 200 is substantially larger than the second taperedsection T2 of the other embodiments. Each of the first and secondtapered sections T1 and T2 may taper along a linear path, an arcuatepath, and a combination thereof. Further, embodiments in which the firsttapered section T1 and/or the second tapered section T2 is omitted arewithin the scope of the present invention. Further, embodiments in whichthe first tapered section T1 extends all the way to the orifice 7thereby omitting the primary compressed fluid channel 13 are within thescope of the present invention. Embodiments in which the second taperedsection T2 extends all the way to the orifice 17 thereby omitting theprimary liquid feed channel 15 are within the scope of the presentinvention.

Optionally, the atomizer 200 may include a combination atomizationchamber and particle dispersion chamber 210 mounted to the housing 202.The chamber 210 is in fluid communication with the atomization means11″. The portion 11″-A of the atomization means 11″ may extend up intothe chamber 210.

The chamber 210 may help define the particle size after the droplets arecreated by and received from the atomization means 11″. The housing 202may include an upper portion 202A having a recessed portion 202B formedalong the inside of the housing defining a lip 202C formed along theoutside of the housing. The chamber 210 includes a housing 216 having aninternal laterally extending wall 216A. The wall 216A has a lowerportion 216B configured to be received inside the recessed portion 202Band maintained in place by the lip 202C when the chamber 210 is mountedto the housing 202.

The wall 216A includes an opening 216C, configured to receive theportion 11″-A of the atomization means 11″ and allow the portion 11″-Ato extend into the chamber 210 thereby allowing the liquid stored in thecontainer 206 and/or external reservoir 300 to be atomized inside thechamber 210. Particles contacting the inside surface of the of thehousing 216 may travel down the wall 216A and into the container 206. Asmention above, liquid in the container 206 may exit therefrom throughthe aperture 206B into the secondary liquid feed channel 5″ forre-atomization by the atomization means 11″.

The chamber 210 includes an atomization chamber-distal output opening216D, and an internal particle dispersion channel 222 communicatingbetween the portion 11″-A of the atomization means 11″ and the outputopening 216D. In some embodiments, the chamber 210 helps impart avelocity vector or flow pattern (e.g., ‘vortical,’ randomized,turbulent, etc. flow) to the aerosolized particles (e.g., atomizedparticles) received within and exiting from the chamber 210. Methods andstructures for imparting a desired velocity vector or flow pattern aredescribed above with respect to the particle dispersion chamber 10 andany methods or structures discussed above may be used with orincorporated into chamber 210.

The atomizer 200 may optionally include the aerodynamic particle-sizefiltering means or filtering member 21 (e.g., air-foil member) suitablyconfigured and positioned at a distance “J” from the primary orificeplane “P” to direct fluid flow around its contour, and therebynon-collisionally redirect particle flow of the desired particle sizerange around its contour, while simultaneously blocking larger particlesfor return to the container 206 and re-entrainment. As is apparent tothose of ordinary skill in the art, the filtering member 21 may beinstalled inside the particle dispersion chamber 210 at distance “J”from the primary orifice plane “P.” Particles filtered from the particleflow may travel down the inside surface of the housing 216, along theinternal laterally extending wall 216A and into the container 206.

The internal channel 222 of the chamber 210 may be configured so as tosustain, and not disrupt, the particle flow or dispersion patterngenerated therein and exiting therefrom through the output opening 216D.Therefore, the internal channel 222 is, for example, cylindrical orsubstantially cylindrical (e.g., slightly tapered), smooth taperedcylindrical, etc., such that there are no abrupt discontinuities alongthe internal surface thereof, or surface structures or elementsextending within the internal channel 222, or end caps, restrictions orelements that restrict the output opening 216D of the channel 222, thatwould disrupt the flow pattern imparted to the particles within theinternal channel 222 and exiting the output opening 216D thereof.

As is apparent to those of ordinary skill, atomizers and nebulizers maybe configured for use with various accessories, adapters, and the likeand the atomizer 200 is not limited to use with any particularaccessories, adapters, and the like. For example, using the techniquesdescribed herein, the nasal adapter 42 (or any adapter described herein)may be coupled to the chamber 210 and configured to receive atomizedparticles from output opening 216D.

Particle Size

As shown in exemplary FIGS. 2-21, the inventive atomization devicesprovide a variable configuration that allows for generating particlessuitable to target, for example, specific areas of the nasal cavity. Inparticular aspects, the variable configuration is associated with thecompressed fluid channel 8 and the liquid/solution feed channel 15. Forexample, in particular embodiments, the adjustment of at least one of“D1,” “D2,” “D3,” “D4,” “D5,” “L1,” “L2,” “L3,” “L4,” “O”, “S,” “A,” “H”and “J” allow for highly efficient generation of particles with, forexample, a MMAD of between about 10 and about 30 microns, and even withsolutions having relatively high viscosity (e.g., up to about 80, or toabout 105 centipoise).

In particular aspects, the delivered atomized particles are comprised ofparticles substantially having a mean diameter of, e.g., 5 μm to 45 μm,5 μm to 50 μm, 7.5 μm to 40 μm, or 10 μm to about 30 μm microns.Typically, for example, about 10 μm to about 30 μm. In some embodiments,the delivered particles are comprised of particles substantially havinga mean diameter of about 10 μm to about 15 μm (e.g., for optimaltargeting the olfactory region and the paranasal sinuses). In otherembodiments, the delivered particles are comprised of particlessubstantially having a mean diameter of about 15 μm to about 30 μm(e.g., for targeting the overall nasal cavity).

According to further aspects, particle size can be varied, and isdetermined by several factors (in addition to the pressure and or volumeof compressed fluid flow) including: the length (“L1” and “L2”) andinternal diameter (e.g., “D1” and “D2”) of the primary compressed fluidfeed 13 and primary liquid feed 15 channels and corresponding orifices 7and 17, respectively; the outer diameter (“D3”) of the primary liquidfeed channel at the orifice end (i.e., the outside diameter of theprimary liquid feed channel end wall face 23); the diameter D4 andlength L3 of the secondary liquid feed channel 5; the distance “H” fromthe primary liquid feed channel end wall face 23 to the primary orificeplane “P” (defined by the primary orifice 7); the angle A of approachbetween the liquid feed channel axis “L” and the compressed fluid feedchannel axis “F”; the selected distance S, as defined herein; the‘offset’ distance O, as defined herein; the distance “J” as definedherein between the particle size filtering member and the primaryorifice plane “P”; and the physical characteristics of the liquid, suchas, surface tension, viscosity, density, etc. Additionally, the design,configuration and spatial placement of the particle size filteringmember or ‘splitter’ and the design (e.g., length, taper, etc) of thedispersion chamber contribute to the particle size.

TABLE 1 illustrates data showing device performance when the nozzlediameter and feed pin angle are changed. The first data set is a 40degree droplet generator where the nozzle diameter is varied from 0.012to 0.015 to 0.0165. The second data set is a group of 0.012 nozzles withthe feed pin angle varied from 40 to 60 degrees in 5 degree intervals.

Therefore, according to particular aspects of the present invention, howconfigurational variables can be adjusted to obtain tailored particlesizes. Similarly, Applicants have shown that: as the inner diameter ofthe feed pin increases the atomization rate and droplet sizes increase;as the height of the feed pin tip increases the atomization ratedecreases; and as the air pressure in the nozzle increase theatomization rate increases and droplet sizes decrease. Therefore theinventive devices offer a substantial improvement in the ability togenerate a broad range of partical sizes.

TABLE 1 Data showing device performance when the nozzle diameter andfeed pin angle are changed. 40 Degree Setup Nozzle D Rate Dv(50) (in)(g/min) (microns) 0.0120 0.58 16.4 0.0150 0.74 19.3 0.0165 0.84 22.00.0120 Nozzle Angle Rate Dv(50) (Degrees) (g/min) (microns) 40 0.5816.44 45 0.63 16.73 50 0.57 15.10 55 0.84 19.12 60 0.86 29.55

In preferred aspects, the inventive integrated devices provideappropriately sized particle distributions having suitable dynamicoutflow properties to target specific areas, such as in the nasal cavityand particular regions thereof, such as the paranasal sinuses, or forocular delivery.

Preferably, the fluid is air or another suitable compressible gas, orcombinations thereof. According to preferred aspects of the presentinvention, the delivered nebulized particles are comprised of particlessubstantially having a mean diameter of about 2 to about 50 μm, about 5to about 50 μm, about 5 to about 40 μm, about 5 to about 35 μm, about 5to about 30 μm, about 5 to about 20 μm, about 5 to about 17 μm, about 5to about 15 μm, about 8 to about 30 μm, about 8 to about 25 μm, about 8to about 20 μm, about 10 to about 30 μm, about 10 to about 25 μm, about10 to about 20 μm, about 10 to about 17 μm, about 10 to about 15 μm,about 11 to about 40 μm, about 11 to about 30 μm, about 11 to about 20μm, about 11 to about 15 μm, about 12 to about 17 μm, about 15 to about25 μm, about 15 to about 20 μm, and about 17 to about 23 μm. Preferably,the delivered nebulized particles are comprised of particlessubstantially having a mean diameter of about 5 to about 30 μm, about 8to about 25 μm, about 10 to about 20 μm, about 10 to about 17 μm, about10 to about 15 μm, and about 12 to about 17 μm. Preferably, thedelivered nebulized particles are comprised of particles substantiallyhaving a mean diameter of about 8 to about 25 μm, about 10 to about 15μm, or about 12 to about 15 μm.

Improved Performance Over the Prior Art

The follow is a discussion comparing the instant devices to those of theprior art in terms of: (A) configurational and operational differences;(B) atomization rates; and (C) efficiency of delivery to, and retentionby, the delivery target.

(A). Configurational and Operational Differences:

The instant novel atomization devices differ from prior art nebulizationand atomization devices in at least nine fundamental ways that give riseto substantially improved performance and utility. However, as isapparent to those of ordinary skill in the art, particular embodimentsof the devices may not include all of these enumerated differences.Further, additional differences beyond those discussed herein exist thatdistinguish one or more of these novel devices from the prior art.

First, the configuration of the atomization means is unique, in that:the primary compressed fluid channel orifice 7 and the primary liquidchannel orifice 17 are separated by at least a distance “H” along theprojected longitudinal axis “F” of the primary compressed fluid feedchannel 13; and the respective projected axes “F” and “L” of the fluidand liquid channels intersect at the angle “A” (e.g., right, or obliqueincluding acute or obtuse). Preferably, the angle “A” is acute.Moreover, in preferred embodiments, at the distance “H”, the plane“I”-intersecting portion 23B of the perimeter 23A of the end-wall face23 is positioned within a selected or selectable distance “S” from theprojected longitudinal axis “F” that is less than or equal to diameter“D1” or less than or equal to ½×D1. This configuration not only affordsa high rate of particle generation, but also affords generation of abroad range of desired MMAD particle size ranges, without the need forprior art impaction/stagnation baffles to violently shatter theparticles providing a relatively limited MMAD particle size range.

Second, in preferred embodiments, the instant devices comprise aparticle filtering member 21 (e.g., an aerodynamic member, for example,an air-foil member) that serves as a particle size filter bynon-collisionally redirecting flow of the desired particle size rangearound its contour while simultaneously blocking larger particles,providing an aerosolized particle filter function that does not rely onimpaction or stagnation baffles to violently shatter impacting dropletsinto the desired particle size range. This feature affords the abilityto provide for a much broader range of MMAD particle size ranges (e.g.,not just the limited ranges attainable using impaction/shattering) bymeans of appropriate design and spatial configuring of the air-foilmember with respect to the atomization means.

Third, because of the inventive positioning of the air-foil or filteringmember 21 relative to the atomization means 11, while larger particlescollide with the filtering member 21, a significant proportion of thedesired size of atomized particles do not collide with the filteringmember 21, and rather follow a non-colliding slightly redirectedparticle flow path along the contour of the filtering member 21. Thisfeature results in relatively faster delivery of the desired particlesbecause they are directed in non-collisional paths toward the user (nocollision, shattering and transverse re-direction as with prior artimpaction/stagnation baffles).

Fourth, in preferred embodiments of the instant devices, the primaryliquid feed channel 15 communicates with the liquid to be nebulized(e.g., in the liquid holding portion of the atomization chamber 4) viaan intermediate secondary liquid feed channel 5 (see in more detailbelow) that is has significantly better flow properties (e.g., largerchannel diameter “D4,” resulting in less drag) than correspondingsecondary liquid feed channels of prior art nebulizers and atomizers,which are relatively constricted (e.g., narrow, with high surface areato cross-section ratios). This affords a substantial improvement overprior art devices, in that the instant devices are capable of generatingparticles from liquids that are significantly more (e.g., 20-30 timesmore) viscous than can be handled by prior art devices.

Fifth, preferred embodiments of the instant devices comprise a particledispersion chamber 10 having a chamber wall 16 and having an inputopening 16B and an output opening 16C with an internal channel 22therebetween, the input opening 16B in fluid communication with theatomization means 11, the dispersion chamber 10 having at least onedirected fluid output 20, 26 operative to impart a fluid flow pattern toaerosolized particles received within and exiting the dispersion chamberoutput opening 16C. By imparting an appropriate flow pattern (e.g.,‘vortical,’ turbulent, randomized, etc.), the particle dispersionchamber 10 provides not only for more effective delivery of aerosolizedparticles, but for effective targeted delivery of the suitably dispersedparticles.

Sixth, preferred embodiments of the instant devices comprise not onlycomprise a nasal 42, 60, and oral adapters 80, that directs particleflow to the respective delivery cavity while preserving the particleflow dynamics (e.g., vortical, turbulent, or randomized flow pattern),but also provide nasal adapters having oriented openings disposed withinthe adapter (e.g., at or near the front or rear of the nose piece) todirect droplet/particle flows into, for example, the front or back partof the nasal aperture (e.g., farthest from, or closest to the lips), orlaterally to the cheeks (oral adapter oriented openings). According toadditionally preferred aspects, such oriented openings providesubstantial additional means to target particle delivery within thenasal and oral cavities of a user.

Seventh, particular embodiments comprise the nasal adapter 60 havingnumerous single flow embodiments as well as dual flow embodiments. Thenasal adapter 60 directs particle flow to the nasal cavity whilepreserving the particle flow dynamics (e.g., vortical, turbulent, orrandomized flow pattern). The exit aperture(s) 60E of the secondinterface portion(s) 60C of the nasal adapter 60 may be configured todirect droplet/particle flows into, for example, the front or back partof the nasal aperture (e.g., farthest from, or closest to the lips).According to additionally preferred aspects, such oriented openingsprovide substantial additional means to target particle delivery withinthe nasal cavity of a user.

Eighth, particular embodiments comprise the ocular adapter 48 tofacilitate ocular delivery of aerosolized particles. For the first time,such embodiments provide for effective targeted delivery of aerosolizedparticles (e.g., medicament-containing aerosolized particles) to auser's eye.

Ninth, particular embodiments comprise the oral adapter 80 to facilitateoral delivery of aerosolized particles. For the first time, suchembodiments provide for effective targeted delivery of aerosolizedparticles (e.g., medicament-containing aerosolized particles) to auser's mouth including the inside surfaces of the cheeks.

(B) Substantially Enhanced Atomization Rate Over the Prior Art:

The atomizer technology described herein may be configured to producesignificantly higher atomization rates and/or efficiencies than priorart jet style atomizers. Without being limited by theory, it is believedthat atomization of the liquid (including higher viscosity liquids)occurs for two primary reasons.

First, the atomized particles or droplets generated travel in arelatively narrow particle stream directed at the nasal opening(s) ofthe user. In contrast, prior art jet style nebulizers, by virtue of theimpactor element, project droplets laterally in a radial path shapedmuch like an umbrella. Therefore, the droplets that are notcollisionally absorbed on the sides of the atomization chamber mustchange direction converge before they can be delivered to, the user.Unfortunately, only a small percentage of the droplets avoid impactingthe inner wall(s) of the jet style nebulizer to be redirected to theuser. Because the droplets of the inventive technology are created by anatomization means that produces a linear droplet stream, the dropsproduced do not need to change direction before exiting the atomizercausing fewer droplets to contact the inner wall(s) thereby allowingmore droplets to exit the device, increasing the atomization rate anddelivery efficiency substantially.

Second, the flow path of the liquid from the reservoir(s) to the pointof droplet generation (e.g., atomization means 11) in the inventivetechnology is significantly less restrictive than that of prior art jetstyle nebulizers. In general, atomization rate, or mass flow rate, maybe determined by at least three factors: (1) the physical properties ofthe liquid; (2) the vacuum pressure created from the venturi effect; and(3) the flow path of the liquid. Therefore, to provide an accuratecomparison of the present technology and jet style nebulizers, the sameliquid and vacuum pressures should be used. Thus, differences in massflow rate may be attributed to differences in the liquid flow paths ofthe devices.

The flow path of the liquid from the reservoir(s) to the point ofdroplet generation (e.g., atomization means 11) in the inventivetechnology differs from that of the prior art jet nebulizers in at leasttwo respects. First, the cross-sectional area of one or more portions ofthe flow path of the instant devices is/are larger than correspondingportion of the flow path in prior art nebulizers. Increasing thecross-sectional area of the flow path, or portions thereof increasesmass flow rate. For example, the cross-sectional area of the secondaryliquid feed channel 5″ is considerably larger than corresponding liquidfeed channels found in prior art nebulizers. Second, the flow path ofthe liquid in the inventive technology has less internal surface areathan the flow path found in prior art nebulizers. In other words, theamount of channel surface engaged by the liquid as it travels from thereservoir to the atomization means is less in the inventive technologythan is found in the prior art. As a fluid flows over a surface, flow ofthe fluid is restricted by shear forces between the fluid and thesurface. The liquid flow path of a typical prior art jet nebulizer, forexample, has approximately three times more surface area than theinventive technology. Therefore, the flow path of a jet nebulizer isthree times more restrictive. Therefore, a linear style atomizer havinga liquid flow path with a larger cross-sectional area and less adjacentsurface area is capable of a higher mass flow rate as well as providingfor atomizing liquids having substantially higher viscosities.

The following TABLE 2 provides data obtained by Applicants comparing theflow rate of the inventive linear nebulizer with a representative priorart jet nebulizer.

TABLE 2 Comparison of flow rate between prior art nebulizer and anexemplary inventive atomizer, and where comparisons are made withliquids of different viscosity. Jet Nebulizer Linear Atomizer Viscosity(grams per minute (grams per minute (centipoise) of inhalation) ofinhalation) 1 0.13 0.42 5 0.06 0.4 10 0 0.35 20 0 0.3 40 0 0.26 60 00.22 80 0 0.18 100 0 0.14

Therefore, not only is the flow rate of the instant inventive atomizerover three times greater than that of the prior art jet nebulizer, butthe instant devices can also deliver fluids having viscosities up to 100centipoise or greater.

(C). Substantially Enhanced Efficiency of Delivery to, and Retention by,the Delivery Target:

The instant devices provide for delivery of multiple optimized bolusesto provide for substantially enhanced delivery to and retention by thedelivery target surfaces.

Prior art spray bottles, for example are typically used to deliver amaximum dose of 1 or 2 boluses of about 0.10 ml per nostril (moreboluses cannot typically be delivered because of saturation of thedelivery target and ‘run-off’. That is, for a variety of reasons amongwhich is the fact the predominant mass of delivered liquid comprisesdrops of relatively large size that collide with the target surface,exceed the saturation point of the tissues and immediately fall off thetissues and drain/run out the nose. In this situation, most of thedelivered agent or drug is actually wasted. In simplistic terms, use ofprior art spray bottles is like throwing ‘water balloons’ of paintagainst at wall, as opposed to spray painting the wall.

By contrast, the instant devices allow for delivery more than 2, andnormally 8 to 15 boluses of droplets each of which may have about 0.01ml of drug, or a greater amount. Because of the optimal size and moreextensive and uniform penetration of the droplets, the droplets arelayered on the tissue multiple times (through multiple inspirations),each droplet finding a surfacr space that is not yet saturated fordeposition (like evenly spray painting a wall without ‘running’ of thepaint). In preferred embodiments, the droplet size is optimized toprovide for delivery of 0.10 ml of drug (per nostril) over 8 to 15inhalation cycles.

Therefore, with respect to the total amount of drug delivered to thenasal cavity, spray bottles, based on the concept above (and as widelyrecognized in the art), maximally deliver about 0.40 ml (two bolussprays of 0.10 ml per nostril). With two nostrils you get the 0.4 ml. Bycontrast, because the instant devices do not have the ‘splatter’ effectwith immediate saturation and run off, the instant devices can in factdeliver much more, depending on the number of inhalation cycles used.Applicants have, for example, determined that the instant devices arecapable of delivering as much as 1 to 1.5 ml without run-off. Accordingto particular aspects, this has substantial and important consequencesfor drug delivery, and particularly for systemic delivery. The abilityto deliver an increase volume of liquid provides for formulations tomove from a suspension to a solution, based on solubility of the activeingredient. Additionally, this capability provides for administration ofcombinations of drugs which previously could not be combined fordelivery due to the requirement to formulate them in a smaller 0.1 mlspray. According to preferred aspects, with the instant devices relativeto the prior art devices, more drug over a larger surface provides forsubstantially more effective topical treatment, as well as greatersystemic absorption.

Nasal mucosa absorption. While not being bound by mechanism, and asrecognized in the art, it is not surprising that a formulated volume ofmore than 0.40 ml could be deposited in the nasal cavities. Generallyspeaking, while the amount and distribution of hygroscopic material onthe surface of the nasal mucosa is difficult to precisely determine andwill depend, at least to some extent on the particular location and time(nasal status). For example, the amount of hygroscopic material maydepend on how a person was breathing (e.g., in/out through the mouth, orthrough the nose). It may additionally depend upon the atmospherictemperature and moisture content, on the composition and amount ofsurface secretions of the nose and their ‘age’ since secretion, and onhow these secretions have been transported across the nasal surface andthus the regional thickness thereof.

Practically speaking, however, and despite the imprecisecharacterization generally available for a particular nasal mucosaregions, the dynamics of the hydration of the mucosa are likely verysignificant in determining the amount of delivery volume that can beabsorbed. A coarse nasal spray, for example, will deliver a quantity oflarge droplets on the surface that will not rapidly be incorporated intothe depths or evenly distribute over the surrounding surface. Rather,the surface becomes locally overburdened, resulting in and run-off. Bycontrast, by delivering a finer spray, local absorption characteristicswill be improved (no immediate saturation) and the surface will be moreuniformly covered relative to the use of larger drops. Additionally,with smaller drops there is a much greater contact area per unit mass ofdrop beneath it and a greater perimeter per unit mass around its edge.Any surface tension-driven spreading of the drop itself would thereforebe more effective, improving the overall rate of absorption per unitmass. Moreover, relative to smaller droplets, larger droplets are moresubject to inertial deposition in the frontal aspects of the airway,whereas finer droplets are more readily travel into the depths of theturbinate region. Furthermore, the imparted particle vector flowprovided by the instant dispersion chambers provides for deeppenetration/delivery in this region. Finally, given a time-gap betweenthe delivered boli of drops (multiple inhalations), there is sufficienttime between breaths for surface absorption and for diffusion into thedepths of the lining material, thus reducing or eliminating run off.

When exposed to water, frank mucus ‘swells’ substantially. For example,if one places an amount of relatively dried up nasal secretion in water,the dried material will substantially swell. Obviously, where such driedmaterial (or partially hydrated material) is distributed over the nasalmucosal surface, it provides a matrix for significant water retention.Where the nasal secretion is less dried out, it would be expected toabsorb water at a different rate compared to a drier sample at the samedegree of swelling.

According to particular aspects, the thickness of a water layerdeposited on the nasal mucosa can be approximated. Given a length of theinner nasal cavity of 8 cm and an overall height of 4 cm, two nasalcavities each having two lateral walls provides for an area of 4×8×2=120cm². Moreover the convolutions of the turbinates would be expected todouble the overall surface area, thus providing an area of about 120 cm²for the whole surface of both nasal cavities. If a 2 ml aliquot wasdistributed uniformly over this surface, it would only be 0.1 mm thick.Where such layer is bound/absorbed to the mucosa beneath, it would notbe expected to run-off to any appreciable extent.

According to further aspects, in the case of relatively insoluble drugs,passage of the carrier water into the mucosal substrate wouldmechanically ‘pull’ ultrafine drug-bearing particles with it, therebyentrapping them in the matrix, holding them in place even if some of thesuspending water was lost (which would be unlikely). According toparticular aspects, labeled water and suspended marked drug particlesare used to show a slower nasal clearance relative to prior art devices.

Particular aspects of the present invention provide method of nasaldelivery of aerosolized particles, comprising: obtaining a subjectinspiring through the nose; delivering, over a plurality of nasalinspirations, aerosolized particles of a liquid formulation into atleast one nasal passage of the subject, wherein a volume in the range of0.2 to 2.0 ml, 0.4 to 1.5 ml, 0.6 to 1.2 ml, 0.8 to 1.1 ml, or 0.9 to 1ml is delivered, wherein the number of inspirations is from about 8 toabout 16, and wherein at least about 30%, about 50%, about 60%, about70%, about 80% about 90% or about 100% of the delivered volume isretained in the at least one nasal passage. In particular embodiments ofthe method, the average tidal volume (V_(t)) is about 0.7 ml/Kg.Applicants note, as appreciated in the art that the tidal volume is thevolume of air inspired into the lungs or expired out of the lungs duringone breath, and that the typical resting value is 500 ml (or about 7ml/kg), increasing dramatically during exercise (e.g., 0.8 to 1.6 L). Incertain embodiments, a volume in the range of about 0.4 to 1.5 ml, 0.6to 1.2 ml, 0.8 to 1.1 ml, or 0.9 to 1 ml is delivered. Applicants note,as appreciated in the art that the ‘respiratory minute volume’ of anaverage subject (in a 70 kg adult, at rest) is approximately 6 L/min. Incertain embodiments between 1 and 3 ml is delivered, wherein the numberof inspirations is from about 16 to about 32, and wherein at least about30%, about 50%, about 60%, about 70%, about 80% about 90% or about 100%of the delivered volume is retained in the at least one nasal passage.

Systemic Delivery Applications

International application PCT/US2004/029001 (published as WO2005/023335) is incorporated herein by reference in its entirety.

Current topical drug delivery methods are ineffective at penetratingvery far into the nasal cavity and not at all into the paranasalsinuses. Further, systemic delivery via inhalation utilizing the nasalmucosa and mucosa in the paranasal sinuses is desired for many targeteddisease states. Preferred aspects of the present invention provide anintegrated nebulizer and particle dispersion chamber apparatus that hasthe ability to deliver the same drugs presently prescribed for manydiseases and conditions as very tiny particle doses of medicine via anasal adapter that allows more efficacious sinus penetration andsystemic delivery for the user.

Examples of diseases that can be treated by systemic delivery with theinventive apparatus and methods include, but are not limited to,endocrine and metabolic disorders, migraines, sleep disorders,autoimmune diseases, osteoporosis, neurological diseases and disorders,obesity, sexual dysfunctions, and cardiovascular diseases and episodes.

According to the present invention, the particle sizes, time ofapplication and particle dispersion technology allow the medicine toreach and permeate the nasal cavity and most of the paranasal sinuses.These factors also allow the medicine to enter the user's system via thenasal cavity. All medicines currently applied by direct action to thenasal cavity and paranasal sinuses could be adapted for use with theinventive integrated nebulizer embodiments, including over-the-counternasal medicines for allergy and colds and flu. Additionally, manymedicines currently taken orally, by skin patch, or parenterally couldbe adapted for use with the inventive integrated nebulizer embodiments.

Significantly, according to the present invention, the integratednebulizer is used for both topical and systemic delivery of drugs,therapeutics and other beneficial compounds.

For a user with a secondary condition of nasal polyps, the inventiveapparatus and methods allow far more effective application of themedicine, which is otherwise blocked or precluded using contemporarysystems. Nasal inhalers and spray bottles used to delivercorticosteroids are designed to also slow the re-growth of polypsfollowing their removal. Currently, however, such devices are largelyineffective at accomplishing this, often not slowing polyp growth atall. According to the present invention, the apparatus and methodsdescribed herein are significantly more effective in slowing polypre-growth following their removal.

Many of the side effects of some medicines are eradicated by theinventive devices and methods. With many sprays, for example, thepropellant causes a drying of the nasal passages leading to bleeds. Withthe use of contemporary devices that lead to bleeds, a secondary sprayof saline is added to the treatment to try and control the bleeding.Furthermore, steroids in pill form have many unpleasant side effectssuch as internal bleeding, a redistribution of fluid to the head, neckand back causing unsightly “humps,” and easy bruising, to name a few. Aneffective use of the inventive integrated nebulizer does not have theseside effects associated with steroids in pill form.

The inventive integrated nebulizer will allow medicine to beadministered to the nasal cavity and paranasal sinuses via very smallparticles that will penetrate deeply into the nasal cavity, most regionsof the paranasal sinuses, and allow for both topical and systemicdelivery. The inventive integrated nebulizer will also provide thepatient with a more effective absorption of the drug, increasingeffectiveness, and will allow multiple conditions to be treated in a farmore effective manner.

Typically, since the medicine is delivered in a treatment and not anattack scenario, the application or delivery time is only 0.5-3 minutes,rather than the 10-15 minutes used during an asthma attack. Multipledose levels of the medicine can be placed in the inventive integratednebulizer, a week supply for example, and the unit will run for aprescribed time, for example but not limited to three minutes, and willthen, in particular embodiments, shut itself off. Preferably, theinventive integrated nebulizer is designed with multiple dose capabilityand a timer with a pause feature. The pause feature allows the user tostop the treatment under way to deal with a short, minor happenstanceand then resume the treatment for the remaining time. The timer isvariable to accommodate the drug being administered and/or prescribed bythe physician.

In preferred aspects, the nasally delivered nebulized particles arecomprised of particles substantially having a mean diameter of about 2to about 50 μm, about 5 to about 50 μm, about 5 to about 40 μm, about 5to about 35 μm, about 5 to about 30 μm, about 5 to about 20 μm, about 5to about 17 μm, about 5 to about 15 μm, about 8 to about 30 μm, about 8to about 20 μm, about 10 to about 30 μm, about 10 to about 25 μm, about10 to about 20 μm, about 10 to about 17 μm, about 10 to about 15 μm,about 11 to about 40 μm, about 11 to about 30 μm, about 11 to about 20μm, about 11 to about 15 μm, about 12 to about 17 μm, about 15 to about25 μm, about 15 to about 20 μm, and about 17 to about 23 μm.

Preferably, the nasally delivered nebulized particles are comprised ofparticles substantially having a mean diameter of about 5 to about 30the delivered nebulized particles are comprises of particlessubstantially having a mean diameter of about 5 to about 30 μm, about 10to about 20 μm, about 10 to about 17 μm, about 10 to about 15 μm, andabout 12 to about 17 μm.

Preferably, the nasally delivered nebulized particles are comprised ofparticles substantially having a mean diameter of about 10 to about 15μm, or about 12 to about 15 μm.

The phrase “substantially having a mean diameter,” as used herein withrespect to preferred particle diameter ranges, refers to the use ofparticle collections, wherein at least 50%, at least 60%, at least 70%,at least 80%, at least 90%, at least 95%, or at least 98% have thepreferred diameter range. Preferably, at least 60%, at least 70%, atleast 80%, at least 90% or at least 95% of the nebulized particles areof the preferred particle diameter range. Preferably, at least 70%, atleast 80%, at least 90% or at least 95% of the nebulized particles areof the preferred particle diameter range.

The foregoing described embodiments depict different componentscontained within, or connected with, different other components. It isto be understood that such depicted architectures are merely exemplary,and that in fact many other architectures can be implemented whichachieve the same functionality. In a conceptual sense, any arrangementof components to achieve the same functionality is effectively“associated” such that the desired functionality is achieved. Hence, anytwo components herein combined to achieve a particular functionality canbe seen as “associated with” each other such that the desiredfunctionality is achieved, irrespective of architectures or intermedialcomponents. Likewise, any two components so associated can also beviewed as being “operably connected,” or “operably coupled,” to eachother to achieve the desired functionality.

While particular embodiments of the present invention have been shownand described, it will be obvious to those skilled in the art that,based upon the teachings herein, changes and modifications may be madewithout departing from this invention and its broader aspects and,therefore, the appended claims are to encompass within their scope allsuch changes and modifications as are within the true spirit and scopeof this invention. It will be understood by those within the art that,in general, terms used herein, and especially in the appended claims(e.g., bodies of the appended claims) are generally intended as “open”terms (e.g., the term “including” should be interpreted as “includingbut not limited to,” the term “having” should be interpreted as “havingat least,” the term “includes” should be interpreted as “includes but isnot limited to,” etc.). It will be further understood by those withinthe art that if a specific number of an introduced claim recitation isintended, such an intent will be explicitly recited in the claim, and inthe absence of such recitation no such intent is present. For example,as an aid to understanding, the following appended claims may containusage of the introductory phrases “at least one” and “one or more” tointroduce claim recitations. However, the use of such phrases should notbe construed to imply that the introduction of a claim recitation by theindefinite articles “a” or “an” limits any particular claim containingsuch introduced claim recitation to inventions containing only one suchrecitation, even when the same claim includes the introductory phrases“one or more” or “at least one” and indefinite articles such as “a” or“an” (e.g., “a” and/or “an” should typically be interpreted to mean “atleast one” or “one or more”); the same holds true for the use ofdefinite articles used to introduce claim recitations. In addition, evenif a specific number of an introduced claim recitation is explicitlyrecited, those skilled in the art will recognize that such recitationshould typically be interpreted to mean at least the recited number(e.g., the bare recitation of “two recitations,” without othermodifiers, typically means at least two recitations, or two or morerecitations).

Accordingly, the claimed invention is not limited except as by theappended claims.

1. An aerosol generating and delivery device comprising: a liquid feedtube having a liquid feed channel with a liquid feed channel exitorifice, an end-wall face and a sidewall, wherein the end wall facebetween the liquid orifice and the perimeter of the liquid feed tube isgenerally normal to a diverting portion of the sidewall of the liquidfeed tube; and a compressed fluid feed channel having a compressed fluidexit orifice, the compressed fluid exit orifice being spaced from adiverting portion of the sidewall, the compressed fluid exit orificebeing configured to direct a stream of compressed fluid toward thediverting portion of the sidewall, the diverting portion of the sidewallbeing configured to disrupt a portion of the stream of compressed fluid,the disrupted portion of the stream of compressed fluid being configuredto atomize a liquid from the liquid exit orifice. 2.-85. (canceled) 86.The device of claim 1, comprising: a reservoir configured to hold aliquid; a liquid supply member comprising a liquid feed tube having asidewall with a diverting portion and comprising a liquid feed channel,the feed channel having an inlet in communication with the reservoir andan liquid supply member exit orifice, the feed channel being configuredto draw liquid from the reservoir and transport it to the exit aperturefor aerosolization therefrom by a compressed fluid; and a compressedfluid supply member comprising a compressed fluid feed channel having anexit orifice, the diverting portion being located between the exitorifice of the liquid feed channel and the exit orifice of thecompressed fluid feed channel, the compressed fluid feed channel beingconfigured to receive a compressed fluid and conduct a portion of thecompressed fluid through the exit orifice and into engagement with thediverting portion of the liquid supply member, the portion of thecompressed fluid engaging the diverting portion being diverted by thediverting portion before aerosolizing the liquid from the exit apertureof the feed channel.
 87. The device of claim 1, wherein the compressedfluid channel and the diverting portion are configured such that asecond portion of the compressed fluid conducted through the compressedfluid exit orifice does not engage the diverting portion of the liquidsupply member.
 88. The device of claim 1, wherein the diverting portionhas a surface, the portion of the compressed fluid engaging thediverting portion engages the surface of the diverting portion, and thesurface is configured to divert the portion of the compressed fluidengaging it non-uniformly.
 89. The device of claim 1, wherein the liquidsupply member comprises a tube section, the feed channel comprises afirst portion disposed inside the tube section, the exit aperture of thefeed channel is formed in the tube section, and the tube sectioncomprises an outside surface, and the diverting portion comprises aportion of the outside surface of the tube section located between theexit orifice of the feed channel and the exit orifice of the compressedfluid channel.
 90. The device of claim 1, wherein the portion of thecompressed fluid conducted through the compressed fluid exit orificeexits the orifice along an axis “F,” the liquid feed channel has alongitudinal axis “L,” and the axis “F” intersects the axis “L.”
 91. Thedevice of claim 1, wherein the liquid feed tube comprises a liquidsupply member comprising a liquid feed channel, the feed channel havingan inlet, a liquid supply member exit orifice, and a supply memberend-wall face having an outside diameter disposed about the liquidsupply member exit orifice, the liquid supply member feed channeldefining a projected axis L, wherein the end wall face liquid feedchannel exit orifice is separated by a distance of at least H from thecompressed fluid channel exit orifice, H being measured along aprojected axis F that is normal to a plane P defined by the compressedfluid channel exit orifice, H is equal to or greater than ¼, ½ or 1× theinner diameter D1 of the compressed fluid channel adjacent thecompressed fluid channel exit orifice, the projected longitudinal axis Lintersects the projected axis F at a right, acute or obtuse angle,defining an intersection plane I, and wherein at the distance H alongprojected axis F, the plane I-intersecting portion of the perimeter ofthe end-wall face is positioned at a distance S in a normal directionfrom the projected axis F, S being equal to or less than 2× the innerdiameter D1 of the primary compressed fluid channel.
 92. The device ofclaim 1, comprising: a reservoir configured to hold a liquid; a liquidsupply member comprising a liquid feed channel comprising: a firstportion with a first diameter and a liquid feed channel exit orifice,and a second portion with a second diameter and an inlet aperture incommunication with the reservoir, the first portion diameter beingsmaller than the second portion diameter, the feed channel beingconfigured to draw liquid from the reservoir into the inlet aperture ofthe second portion and transport it to the exit orifice of the firstportion for aerosolization therefrom by a compressed fluid; and acompressed fluid supply member comprising a compressed fluid channel andcompressed fluid channel exit orifice configured to direct a compressedfluid flow passed the exit orifice of the first portion of the feedchannel thereby aerosolizing the liquid therefrom.
 93. The device ofclaim 1, comprising: a housing having a wall defining an atomizationchamber in which a liquid or solution is atomizable, and comprisingholding means suitable for holding a liquid or solution to be atomized;and atomization means comprising a primary compressed fluid feed channelhaving a length and inner diameter, and a primary compressed fluid exitorifice at a first end thereof in fluid communication with theatomization chamber and defining a primary compressed fluid exit orificeplane P, the channel at a second end in fluid communication with acompressed fluid source and defining a projectable compressed fluid feedchannel axis F, the atomization means further comprising a primaryliquid feed channel having a length, inner diameter and channel wall,and at a first channel end having a channel end-wall face having anoutside diameter disposed about a liquid feed channel orifice in fluidcommunication with the atomization chamber, the primary liquid feedchannel at a second end in communication with the liquid holding means,the primary liquid feed channel defining a projectable longitudinalliquid feed channel axis L, wherein the channel end wall face and theliquid feed channel orifice are separated by a distance of at least Hfrom the primary orifice plane P, H being measured along the projectedaxis F and H being equal to or greater than ¼, ½ or 1× the innerdiameter D1 of the primary compressed fluid feed channel, wherein theprojected longitudinal axis L intersects the projected longitudinal axisF at a right, acute or obtuse angle, defining an intersection plane I,and wherein at the distance H along projected longitudinal axis F, theplane I-intersecting portion of the perimeter of the end-wall face ispositioned at a distance S in a normal direction from the projectedlongitudinal axis F, S being equal to or less than 2× the inner diameterD1 of the primary compressed fluid feed channel.
 94. The device of claim93, further comprising a secondary liquid feed channel having a lengthand an inner diameter D4, and communicating between the second end ofthe primary liquid feed channel and the liquid holding means, whereinthe inner diameter D4 is larger than the inner diameter D2 of theprimary liquid feed channel.
 95. The device of claim 93, wherein theselected distance S is such that there is overlap of axis F with theplane I-intersecting portion of the perimeter of the end wall face,wherein overlap is defined as being present if the projected axis Fintersects the end wall face or the liquid feed channel orifice thereof.96. The device of claim 1, wherein the atomized liquid comprisesparticles, and the device further comprises a filtering memberconfigured aerodynamically to filter particles from the atomized liquidhaving a size greater than a predetermined maximum size.
 97. The deviceof claim 96, wherein the particle filter member is in fluidcommunication with the particle atomization means, the particle filtermember having a surface contour and positioned at a distance of at leastJ along a projected axis F from the primary orifice plane P to providean aerodynamic fluid flow around the surface, and wherein the particlefilter member is held at the distance J along the projected axis F by atleast one filter support member communicating with the wall of theatomization chamber, the support member configured to operatively directliquid accumulating on the filter away from the filter member for returnto the liquid holding means.
 98. The device of claim 1, furthercomprising a particle dispersion chamber configured to receive theatomized liquid and impart a predetermined flow pattern thereto,preferably wherein the imparted fluid flow pattern is at least one ofvortical flow, turbulent flow and randomized flow.
 99. The device ofclaim 98, wherein the particle dispersion chamber comprises a chamberwall and an input opening and an output opening with an internal channeltherebetween, the input opening in fluid communication with theatomization chamber, the dispersion chamber having at least one directedfluid output configured to impart a fluid flow pattern to aerosolizedparticles within and exiting the dispersion chamber output opening. 100.The device of claim 99, additionally comprising: a secondary compressedfluid channel intermediate between the primary compressed fluid feedchannel and a source of compressed fluid; and a particle dispersionchamber feed channel communicating between the secondary compressedfluid channel and the at least one directed compressed fluid outlets andcorresponding orifices.
 101. The device of claim 1, further comprising anasal, ocular, oral or vicinity adapter in communication with theatomization means.
 102. The device of claim 1, wherein the liquid foratomization comprises at least one selected from the group consisting ofmedicaments, small or large molecule pharmaceutical agents, liquids,solutions, suspensions, emulsions, perfumes, fragrances, essential oils,cosmeceutical agents, oils, cosmeceutical agents, moisturizing agents,water, lotions, air fresheners, deionizing agents, aromatherapeuticagents, beverages, and skin treatments.
 103. The device of claim 1,wherein the liquid feed tube comprises a liquid feed channel having aninternal diameter D2 at the liquid feed channel exit orifice, thecompressed fluid feed channel having an internal diameter D1 at thecompressed fluid exit orifice, and wherein D2 is equal to or greaterthan D1.
 104. A method for generating and delivering an aerosol,comprising: providing a liquid in a liquid feed tube having a liquidfeed channel with a liquid feed channel exit orifice, an end-wall faceand a sidewall, wherein the end wall face between the liquid orifice andthe perimeter of the liquid feed tube is generally normal to a divertingportion of the sidewall of the liquid feed tube; and directing apressurized fluid through a compressed fluid feed channel having acompressed fluid exit orifice, the compressed fluid exit orifice beingspaced from a diverting portion of the sidewall, the compressed fluidexit orifice being configured to direct a stream of compressed fluidtoward the diverting portion of the sidewall, the diverting portion ofthe sidewall being configured to disrupt a portion of the stream ofcompressed fluid, the disrupted portion of the stream of compressedfluid being configured to atomize a liquid from the liquid exit orifice,wherein generating and delivering an aerosol is afforded.